A Multi-Center Study to Characterize the Long-Term Safety and Efficacy of BMS-986165 in Subjects With Systemic Lupus Erythematosus
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Multi-Center Study to Characterize the Long-Term Safety and Efficacy of BMS-986165 in 
Subjects with Systemic Lupus Erythematosus 
 
NCT Number: NCT03920267 
Document Date (Date in which document was last revised): 15 Jan 2021 
 
 
 

Page:
1
Protocol Number:
IM011074
Date, Version:
15-Jan-2021, Revised Protocol 3 Final Approved
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND: 134,253
EudraCT: 2018-003471-35
Ex-US: Non-IND
CLINICAL PROTOCOL IM011074
A Multi-Center Study to Characterize the Long-Term Safety and Efficacy of BMS-986165 in 
Subjects with Systemic Lupus Erythematosus
Short Title:  Long-Term Safety and Efficacy of BMS-986165 in Subjects with Systemic Lupus 
Erythematosus
Clinical Trial Physician
Medical Monitor- Americas
Medical Monitors- EAPA
 
Bristol-Myers Squibb Company
3401 Princeton Pike
Lawrenceville, NJ 08648 USA
PRA Health Sciences
4130 ParkLake Avenue
Ste 400
Raleigh, NC 27612 USA
PRA Health Sciences 
500 South Oak Way
Reading, Berkshire, RG2 6AD, 
United Kingdom
 
PRA Health Sciences
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Nucleos North Tower
Singapore 138567
Telephone (ofc): 
Fax: 
Telephone (ofc): 
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Telephone (ofc): 
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North America: +1-866-326-5053 or +1-434-951-4082
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Bristol-Myers Squibb Company
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Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
6-5-1 Nishi-Shinjuku, Shinjuku-ku,
Tokyo, 163-1328, Japan
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This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations, eg, a Contract Research Organization.
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DOCUMENT HISTORY
Document
Date of Issue
Approver(s)
Summary of Change
Revised 
Protocol 3
(Revision 3, 
Version 4.0a)
(im011074-
revprot03)
15-Jan-2021
-Included a safety follow-up visit at the
end of the study
-Changed the on-treatment portion of the
study from 108 weeks to 174 weeks
-Allowed subjects who experience a
disruption in treatment due to exceptional 
circumstances after completion of the 
parent study, IM011021, to enter the 
IM011074 long-term extension (LTE)
Revision 2, 
Version 3.0
(im011074-
revprot02)
12-Feb-2019
Clarified additional blood samples to be 
collected for BILAG scoring
Revision 1, 
Version 2.0
(im011074-
revprot01)
14-Dec-2018
Included LLDAS response as an additional 
endpoint, allowed a larger window for 
selected visits, described treatment 
assignment details
 
 
 
Original Protocol
(im011074-prot)
26-Oct-2018
Not applicable
a Document naming conventions have been updated. Legacy PRA numbering is provided for consistency.
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 03:
The primary purpose of this revised protocol is to include the following updates:

To include a safety follow-up visit at the end of the study

To change the on-treatment portion of the study from 108 weeks to 174 weeks

To allow subjects who experience a disruption in treatment due to exceptional circumstances
after completion of the parent study, IM011021, to enter the IM011074 long-term extension
(LTE)
This revised protocol will be implemented after the Investigator receives all appropriate agency 
and IRB/EC approvals.
Generally, only major additions and deletions are provided in this summary of changes document, 
and all minor grammatical, formatting, rephrasing, stylistic changes, or clarifications, as well as 
reorganizational changes are not included. All changes applied to the protocol body were applied 
to the protocol synopsis, as necessary; synopsis changes are not included in the summary of key 
changes table.
The rationale for the change to this Revised Protocol is provided in the summary of key changes 
table, as shown below:
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of Change
Brief Rationale
Study Acknowledgment 
/Disclosure
This page was removed.
To align with BMS protocol 
standards, this page is now provided 
as a standalone component.
Section 1.3, Schedule of 
Activities (SOA)
Section 4, Study Design
Figure 1, IM011074 Study 
Design
Section 7.1, Discontinuation 
from Study Treatment
Section 8.5.1, Sampling 
Schedule
The last treatment visit for 
nondiscontinuing subjects was 
changed from Week 108 to 
Week 174. A follow-up (end-of-
study) visit was added at Week 178.
Timing of assessments was adapted 
to the increased number of weeks and 
visits where applicable.
To provide an additional 66 weeks of 
therapy and to add a follow-up
(end-of-study) visit for subject safety 
Section 4.1.2.1, Data Monitoring 
Committee
The timing of the data monitoring 
committee’s planned meetings was 
removed.
To remove potential incongruity as 
these details are listed in the data 
monitoring committee’s charter.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of Change
Brief Rationale
Section 5.1, Inclusion Criteria
Inclusion criterion 2)a was updated 
to allow subjects experiencing 
exceptional circumstances to 
participate in the LTE with sponsor 
approval.
To allow inclusion of subjects (with 
approval from the BMS Clinical 
Trial Physician) who are willing to 
participate in the study but cannot 
meet some original requirements.
Several reproductive status–related 
inclusion criteria were updated.
To align reproductive status–related 
criteria with those in the parent 
study, IM011021, and the
sponsor-approved guidelines specific 
to the BMS-986165 program.
Section 5.3, Lifestyle 
Restrictions
Fasting requirements were removed;
and the suggestion that caffeine, 
alcohol, tobacco, and activity should 
be limited was removed.
To reduce unnecessary 
inconvenience to subjects based on 
updated sponsor-approved guidelines
specific to the BMS-986165 program
and to align with Section 8.4.4.
Section 6.3.2, Circumstances for 
Unblinding
The clarification that certain 
members of the BMS study team 
would be partially unblinded after 
database lock of the parent study was 
added.
To clarify IM011074 remains 
blinded to investigators, site 
personnel, and subjects if and when 
the parent study, IM011021, is 
unblinded to some members of the 
BMS study team.
Section 6.7.1, Prohibited and/or 
Restricted Treatments
The restriction on initiating topical 
corticosteroid use was removed. 
NSAID dosing restrictions are 
reduced during the study.
To reduce the restriction on topical 
corticosteroids and the need for 
continuation of NSAIDs in 
IM011074 if indicated medically.
Section 7.1.2, Post-study 
Treatment Follow-up
Definitions of the end-of-treatment 
visit and end-of-study visit for 
subjects who do not complete the 
study were clarified.
To clarify, for data analysis purposes, 
which visits should be considered 
end-of-treatment and end-of-study
for subjects who discontinue early.
Section 8.1.1.5, SLE Responder 
Index (SRI[4])
The fourth requirement to fulfill the 
SRI(4) composite endpoint was 
removed.
To align with the parent protocol and 
original publication for SRI.
Section 8.2.1 (new), Adverse 
Events of Interest
A section outlining potential adverse 
events of interest (AEIs) was added.
To allow for additional information 
collection throughout the study 
regarding potential AEIs, which are 
collected across the BMS-986165
program.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of Change
Brief Rationale
Section 8.4.3, Tuberculosis 
Assessment
Procedures for subjects who are at 
increased risk for tuberculosis were 
clarified.
To clarify that subjects who are at 
increased risk for tuberculosis can 
potentially roll over into the study 
from the parent study but must have 
an interferon gamma release assay 
(IGRA) at Week 0.
Section 8.4.4, Clinical Safety 
Laboratory Assessments
The fasting glucose assessment was 
replaced with nonfasting glucose,
and the fasting lipid panel was
removed.
To reduce unnecessary 
inconvenience related to fasting 
glucose assessment and fasting lipid 
panel, which are no longer necessary 
assessments.
Section 9.1, Sample Size 
Determination
Additional details related to the 
sample size determination were 
added.
To add 95% CI information.
Section 9.2, Populations for 
Analyses
The definition of the ‘As-treated’ 
population was clarified to include 
subjects who took study treatment
other than the treatment he or she 
was assigned.
To clarify data analysis procedures 
for subjects who did not take the 
same dose they were assigned.
Appendix 4, Women of 
Childbearing Potential 
Definitions and Methods of 
Contraception
Contraception guidance for female 
and male subjects was updated.
To align contraception guidance with 
guidance in the parent study, 
IM011021, and the sponsor-approved 
guidelines specific to the 
BMS-986165 program.
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 03: ............................ 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 ................ 
TABLE OF CONTENTS .............................................................................................. 
LIST OF TABLES ........................................................................................................ 
LIST OF FIGURES ...................................................................................................... 
1 PROTOCOL SUMMARY ......................................................................................... 
1.1 Synopsis ............................................................................................................ 
1.2 Schema .............................................................................................................. 
IM011074 Study Design .................................................................................... 
1.3 Schedule of Activities (SOA) ........................................................................... 
2 INTRODUCTION ..................................................................................................... 
2.1 Study Rationale ................................................................................................. 
2.2 Background ....................................................................................................... 
2.2.1 Early Clinical Development ..................................................................... 
2.3 Benefit/Risk Assessment .................................................................................. 
3 OBJECTIVES AND OUTCOME MEASURES ....................................................... 
4 STUDY DESIGN....................................................................................................... 
4.1 Overall Design .................................................................................................. 
4.1.1 Qualification ............................................................................................ 
4.1.1.1 Treatment Allocation ...................................................................... 
4.1.2 Data Monitoring Committee 
 ................ 
4.1.2.1 Data Monitoring Committee ........................................................... 
 ................................................................. 
4.2 Number of Subjects ........................................................................................... 
4.3 End of Study Definition .................................................................................... 
4.4 Scientific Rationale for Study Design............................................................... 
4.5 Justification for Dose ........................................................................................ 
5 STUDY POPULATION ............................................................................................ 
5.1 Inclusion Criteria .............................................................................................. 
5.2 Exclusion Criteria ............................................................................................. 
5.3 Lifestyle Restrictions ........................................................................................ 
5.3.1 Meals and Dietary Restrictions ............................................................... 
5.3.2 Caffeine, Alcohol and Tobacco ................................................................ 
5.3.3 Activity ..................................................................................................... 
6 TREATMENT ........................................................................................................... 
6.1 Treatments Administered .................................................................................. 
6.2 Method of Treatment Assignment .................................................................... 
6.3 Blinding............................................................................................................. 
6.3.1 Maintaining the Blind .............................................................................. 
6.3.2 Circumstances for Unblinding ................................................................. 
6.4 Dosage Modification ......................................................................................... 
6.5 Preparation/Handling/Storage/Accountability .................................................. 
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6.5.1 Retained Samples for Bioavailability/Bioequivalence ............................. 
6.6 Treatment Compliance ...................................................................................... 
6.7 Concomitant Therapy........................................................................................ 
6.7.1 Prohibited and/or Restricted Treatments................................................. 
6.7.2 Permitted Concomitant Medications ....................................................... 
6.7.3 Existing Therapies for Systemic Lupus Erythematosus ........................... 
6.7.4 Corticosteroid Treatment ......................................................................... 
6.8 Treatment After the End of the Study ............................................................... 
7 DISCONTINUATION CRITERIA ........................................................................... 
7.1 Discontinuation from Study Treatment ............................................................ 
7.1.1 Temporary Discontinuation of Study Medication .................................... 
7.1.2 Post-study Treatment Follow-up.............................................................. 
7.2 Discontinuation from the Study ........................................................................ 
7.3 Lost to Follow-Up ............................................................................................. 
8 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
8.1 Efficacy Assessments ........................................................................................ 
8.1.1 Investigator-Administered Assessments ................................................... 
8.1.1.1 British Isles Lupus Assessment Group (BILAG)-2004 ................... 
8.1.1.2 Systemic Lupus Erythematosus Disease Activity Index 2000 
(SLEDAI-2K)......................................................................................... 
8.1.1.3 Cutaneous Lupus Erythematosus Disease Area and Severity Index 
(CLASI) ................................................................................................. 
8.1.1.4 40-joint Count ................................................................................. 
8.1.1.5 SLE Responder Index (SRI[4]) ....................................................... 
8.1.1.6 BILAG-based Composite Lupus Assessment (BICLA) .................... 
8.1.1.7 Physician’s Global Assessment (PGA) of Disease Activity ............ 
8.1.1.8 SLE Flares ...................................................................................... 
8.1.1.9 Systemic Lupus Erythematosus International Collaborating Clinics 
/ American College of Rheumatology Damage Index (SDI) ................. 
8.1.1.10 Lupus Low Disease Activity State (LLDAS).................................. 
8.1.2 Subject-Reported Assessments ................................................................. 
8.1.2.1 Patient-Reported Outcomes Measurement Information System 
(PROMIS) Fatigue ................................................................................ 
8.2 Adverse Events ................................................................................................. 
8.2.1 Adverse Events of Interest ........................................................................ 
8.2.2 Time Period and Frequency for Collecting AE and SAE Information .... 
8.2.3 Method of Detecting AEs and SAEs ......................................................... 
8.2.4 Follow-up of AEs and SAEs ..................................................................... 
8.2.5 Regulatory Reporting Requirements for SAEs ......................................... 
8.2.6 Pregnancy ................................................................................................ 
8.2.7 Laboratory Test Result Abnormalities ..................................................... 
8.2.8 Potential Drug-Induced Liver Injury (DILI) ............................................ 
8.2.9 Other Safety Considerations .................................................................... 
8.3 Overdose ........................................................................................................... 
8.4 Safety ................................................................................................................ 
8.4.1 Physical Examinations ............................................................................. 
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8.4.2 Vital Signs ................................................................................................ 
8.4.3 Tuberculosis Assessment .......................................................................... 
8.4.4 Clinical Safety Laboratory Assessments .................................................. 
8.5 Pharmacokinetics .............................................................................................. 
8.5.1 Sampling Schedule ................................................................................... 
8.5.2 Sampling Windows ................................................................................... 
8.6 Exploratory Biomarker Assessments ................................................................ 
 .............................................................. 
8.6.2 Additional Research Collection ............................................................... 
8.7 Health Economics OR Medical Resource Utilization and Health Economics . 
9 STATISTICAL CONSIDERATIONS....................................................................... 
9.1 Sample Size Determination ............................................................................... 
9.2 Populations for Analyses .................................................................................. 
9.3 Endpoints .......................................................................................................... 
9.3.1 Safety Assessments – Primary Endpoint .................................................. 
9.3.2 Secondary Endpoints ............................................................................... 
9.3.3 Additional Endpoints ............................................................................... 
9.3.4 PK Endpoints ........................................................................................... 
9.3.5 PD Endpoints ........................................................................................... 
9.4 Efficacy Analyses ............................................................................................. 
9.5 Safety Analyses ................................................................................................. 
9.5.1 Adverse Events ......................................................................................... 
9.5.2 Vital Signs, and Physical Examinations .................................................. 
9.5.3 Clinical Laboratory Tests ........................................................................ 
9.6 Other Analyses .................................................................................................. 
9.6.1 Demographics and Baseline Data ........................................................... 
9.6.2 Prior and Concomitant Medications ....................................................... 
9.6.3 Pharmacokinetics ..................................................................................... 
9.6.4 Exploratory Biomarkers ........................................................................... 
9.7 Interim Analyses ............................................................................................... 
10 REFERENCES ........................................................................................................ 
11 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP AND REPORTING ........................................................................ 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
APPENDIX 5 BRITISH ISLES LUPUS ASSESSMENT GROUP (BILAG)-2004.... 
APPENDIX 6 SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY 
INDEX 2000 ........................................................................................................... 
APPENDIX 7 CUTANEOUS LUPUS ERYTHEMATOSUS DISEASE AREA AND 
SEVERITY INDEX (CLASI)................................................................................. 
APPENDIX 8 VISUAL ANALOG SCALE FOR PHYSICIAN’S GLOBAL 
ASSESSMENT OF DISEASE ACTIVITY............................................................ 
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APPENDIX 9 SYSTEMIC LUPUS INTERNATIONAL COLLABORATING 
CLINICS/ AMERICAN COLLEGE OF RHEUMATOLOGY DAMAGE INDEX
................................................................................................................................. 
APPENDIX 10 PATIENT-REPORTED OUTCOMES MEASUREMENT 
INFORMATION SYSTEM (PROMIS) FATIGUE ............................................... 
APPENDIX 11 TUBERCULOSIS RISK ASSESSMENT TOOL ............................... 
 
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LIST OF TABLES 
Table 1: On-Treatment Procedural Outline (IM011074): Week 0 through Week 96 ... 
Table 2: On-Treatment Procedural Outline (IM011074): Week 108 through Week 174
................................................................................................................................. 
Table 3: Objectives and Outcome Measures ................................................................ 
Table 4: Study Treatments for IM011074 .................................................................... 
Table 5: Selection and Timing of Dose ........................................................................ 
Table 6: Pharmacokinetic Sampling Schedule for BMS-986165 ................................. 
Table 7: Residual Sample Retention for Additional Research Schedule ...................... 
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LIST OF FIGURES 
 
Figure 1: IM011074 Study Design ............................................................................... 
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PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Multi-Center Study to Characterize the Long-Term Safety and Efficacy of 
BMS-986165 in Subjects with Systemic Lupus Erythematosus
Short Title: Long-Term Safety and Efficacy of BMS-986165 in Subjects with Systemic Lupus 
Erythematosus
Study Phase: 2
Rationale:
BMS-986165 is the first, potent, oral tyrosine kinase 2 (TYK2) inhibitor with a novel, highly 
selective mechanism of action that has the potential to safely and effectively treat a broad spectrum 
of autoimmune diseases. TYK2 activates intracellular signal transducer and activator of 
transcription (STAT)-dependent transcription and functional responses downstream of receptors 
for critical immune mediators, such as interleukin (IL)-12, IL-23, and Type I and III interferons 
(IFNs). These immune and inflammatory signaling pathways are critical in the pathophysiology 
of various immune-mediated diseases including psoriasis, lupus, spondyloarthritis, inflammatory 
bowel disease (IBD), dermatomyositis, and type I interferonopathies. BMS-986165 potently 
inhibits IL-23-, IL-12-, and type I/III IFN-driven responses and has demonstrated proof of 
mechanism in mouse models of autoimmunity (psoriasis, colitis, and systemic lupus 
erythematosus [SLE]) and in healthy humans.
Inhibition of TYK2 is expected to provide therapeutic benefit for subjects with SLE for multiple 
reasons: 1) The major pathways in the TYK2 signaling cascade (Type 1 IFN and IL-12/23 and the 
downstream mediators IFNγ and IL-17) have been implicated in SLE disease pathogenesis; 2) It 
is conceivable that TYK2 inhibition may show improved benefits over existing anti-IFN 
monoclonal antibody therapies currently in development because of combined blocking effects on 
both the IL-12/23 and Type 1 IFN pathways. 
A Phase 2 study (IM011021) of BMS-986165 in the treatment of SLE is ongoing. This long-term 
extension (LTE) study will provide additional safety, efficacy, and patient-reported outcome 
(PRO) data of BMS-986165 in subjects who complete IM011021. 
Study Population:
Subjects with SLE who have completed the protocol-required treatment period in BMS-986165 
protocol IM011021 will be eligible to participate.
Objectives and Outcome Measures:
Objective
Outcome Measure
Primary
Safety

To characterize the long-term safety and 
tolerability of BMS-986165 in subjects with SLE

Adverse events and serious adverse events, vital 
sign measurements, and laboratory parameters
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Objectives and Outcome Measures:
Objective
Outcome Measure
Additional
Efficacy

To characterize the long-term maintenance of 
response of BMS-986165 in the treatment of 
subjects with SLE

CLASI response

40-joint count for tender, swollen, and tender + 
swollen joints

SRI(4) response

BICLA response

PGA

Corticosteroid use (yes/no)

Corticosteroid dose ≤7.5 mg/day (yes/no)

Flare Analysis
o
Time to first flare
o
Number and frequency of flares
o
Flares leading to hospitalization

SDI total score

BILAG response

SLEDAI-2K score

LLDAS response

To characterize patient-reported outcomes in 
subjects with SLE on long-term BMS-986165 
therapy

PROMIS Fatigue Short Form 7a score
Pharmacokinetic

To explore long-term pharmacokinetics of 
BMS-986165

Plasma concentrations of BMS-986165
Pharmacodynamic

To explore long-term pharmacodynamics of 
BMS-986165

dsDNA, CRP, Complement levels, UPCR
BICLA = BILAG-based Composite Lupus Assessment; BILAG = British Isles Lupus Assessment Group; CLASI = 
Cutaneous Lupus Erythematosus Disease Area and Severity Index; CRP = C-reactive protein; dsDNA = double 
stranded deoxyribonucleic acid; LLDAS = Lupus Low Disease Activity State; PGA = Physician’s Global Assessment; 
PROMIS = Patient-Reported Outcomes Measurement Information System; SDI = Systemic Lupus Erythematosus 
International Collaborating Clinics / American College of Rheumatology Damage Index; SLEDAI-2K = Systemic 
Lupus Erythematosus Disease Activity Index 2000; SLE = systemic lupus erythematosus; SRI(4) = Systemic Lupus 
Erythematosus Responder Index; UPCR = urine protein/creatinine ratio
Overall Design:
This will be a multi-year, multi-center study to evaluate the long-term safety and tolerability of 
BMS-986165 in subjects who have completed the Phase 2 SLE study IM011021. Subjects who 
complete IM011021 through Week 48 will be offered the opportunity to continue to IM011074. 
The final treatment visit for IM011021 and the relevant procedures performed, will serve as the 
Week 0 visit and assessments, respectively, for IM011074. Procedures will not be duplicated 
between the IM011021 Week 48 treatment visit and the Week 0 visit of this protocol. 
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BMS-986165
TYK2 Inhibitor
In this longitudinal study, qualified subjects from the Phase 2 study IM011021 will receive blinded 
BMS-986165 at the same oral dose (12 mg once daily [QD], 6 mg twice daily [BID], or 3 mg BID) 
as the subjects received at the time of completion of IM011021. Those receiving placebo in 
IM011021 will be randomized 1:1:1 to one of the active blinded treatment doses. 
All subjects will return to the clinic for assessments every 4 weeks for the first 12 weeks, with 
subsequent visits occurring every 12 to 14 weeks through the end of treatment (EOT; Week 174
or early discontinuation). An additional visit will occur at Week 44 to ensure an appropriate 
comparator visit for the Week 48 efficacy assessments. Investigator- and subject-administered 
endpoint assessments will be performed at each scheduled clinic visit through the EOT visit 
(Week 174 or early discontinuation); subjects will return to the clinic 28 days after the EOT visit 
for a safety follow-up visit. Unscheduled visits will be allowed throughout the study period as 
needed for additional safety monitoring. Adjustments to subjects’ background SLE therapy will 
be considered after consultation by the investigator with the Medical Monitor(s).
Number of Subjects:
The total number of subjects will be based on the number that complete IM011021 and continue 
into IM011074.
Treatment Arms and Duration: 
Study treatment: Subjects in all treatment groups of the parent study IM011021 that enroll in 
IM011074 will take oral doses of the investigational product (IP) for the duration of the study as 
follows: BMS-986165 12 mg QD, BMS-986165 6 mg BID, or BMS-986165 3 mg BID. Those 
receiving placebo in IM011021 will be randomized 1:1:1 to one of the aforementioned active 
blinded treatment doses. 
Study Treatments for IM011074
Medication 
Potency 
IP/Non-IP 
BMS-986165 tablet 
3 mg
IP
BMS-986165 tablet 
6 mg
IP
BMS-986165 tablet 
12 mg
IP
Placebo
n/a
IP
IP = investigational product; n/a = not applicable
Statistical Considerations
Sample Size and Power Determination:
As the primary purpose of this study is to understand the longer term safety of BMS-986165 in 
patients with SLE who have completed the parent study (IM011021), no formal calculations of 
sample size and power determination were made. All qualified subjects who complete the final 
treatment visit from the parent SLE study IM011021 will be eligible to participate.
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General Methodology:
The ‘as-treated’ population will be used to summarize subject data. The ‘as-treated’ population 
will include all subjects enrolled in the LTE study who took at least one dose of study treatment 
during the LTE study. 
The treatment group ‘as-treated’ will be the same as the treatment group the subjects were assigned 
to in this study, except in the following cases:

If a subject took the same incorrect treatment throughout this study, then the subject will be
analyzed based on the treatment received.

If a subject took study drug from more than one treatment group, and none of the
administrations were consistent with the assigned treatment group, then the subject will be
analyzed based on the first treatment taken.
Data will be summarized descriptively at each timepoint and by treatment group. Categorical data 
will be summarized as frequency counts and percentages. Continuous data will be summarized 
using n, mean, standard deviation, median, minimum, and maximum unless otherwise specified. 
1.2
Schema
IM011074 Study Design 
Abbreviations: 
BID 
= 
twice 
daily; 
FU 
= 
follow-up;
QD 
= 
once 
daily;
R 
= 
randomize 
Note: For illustrative purposes only. Due to the long treatment period, the number of weeks represented and the 
distances between hashmarks are not to scale.
1.3
Schedule of Activities (SOA)
The schedules of assessments and procedures for Weeks 0 through 96 and Weeks 108 through 174
are documented in Table 1 and Table 2, respectively.
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TYK2 Inhibitor
Table 1:
On-Treatment Procedural Outline (IM011074): Week 0 through Week 96
Procedure
Wk 0
D1a
Wk 4
D29
±3d 
Wk 8
D57
±3d
Wk 12
D85
±3d
Wk 24
D169
±7d
Wk 36
D253
±7d
Wk 44
D309
±3d
Wk 48
D337
±3d
Wk 60
D421
±7d
Wk 72
D505
±7d
Wk 84
D589
±7d
EOT 1b
Wk 96
D673
or ET
±7d
Notes
Eligibility
X
Safety Assessments
Complete Physical 
Examination
X
X
X
General, head, eyes, 
ears, nose, throat, neck, 
CV, lungs, abdominal, 
extremities, neurologic, 
psychiatric, skin, 
musculoskeletal
Targeted Physical 
Examination
X
X
X
X
X
X
X
X
X
General, eyes, throat, 
CV, lungs, abdominal, 
extremities, skin, 
musculoskeletal, and 
others as clinically 
indicated
Body Weight
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
X
AE Assessment
Xc
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medication 
Use
X
X
X
X
X
X
X
X
X
X
X
X
History of Tobacco Use
X
Include description of 
current tobacco use
Corticosteroid Use 
Assessment
X
X
X
X
X
X
X
X
X
X
X
X
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Table 1:
On-Treatment Procedural Outline (IM011074): Week 0 through Week 96
Procedure
Wk 0
D1a
Wk 4
D29
±3d 
Wk 8
D57
±3d
Wk 12
D85
±3d
Wk 24
D169
±7d
Wk 36
D253
±7d
Wk 44
D309
±3d
Wk 48
D337
±3d
Wk 60
D421
±7d
Wk 72
D505
±7d
Wk 84
D589
±7d
EOT 1b
Wk 96
D673
or ET
±7d
Notes
Laboratory Tests
Hematology 
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry Panel
X
X
X
X
X
X
X
X
X
X
X
X
Include CK
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
UPCR
X
X
X
X
X
X
X
X
X
X
X
X
Coombs Test (direct)
X
X
X
X
X
X
X
X
X
X
X
X
Blood samples for 
hemolysis confirmation
X
X
X
X
X
X
X
X
X
X
X
X
Haptoglobin and 
reticulocyte count
hs-CRP
X
X
X
X
X
X
X
X
X
X
TB Questionnaire
X
X
X
IGRA for increased-risk 
subjects
Pregnancy Test (Urine)
X
X
X
X
X
X
X
X
X
X
X
X
WOCBP only
Biomarker Assessments
Serum Complement
X
X
X
X
X
X
X
X
X
X
X
X
Anti-dsDNA autoantibodies
X
X
X
X
X
X
X
X
X
X
X
X
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TYK2 Inhibitor
Table 1:
On-Treatment Procedural Outline (IM011074): Week 0 through Week 96
Procedure
Wk 0
D1a
Wk 4
D29
±3d 
Wk 8
D57
±3d
Wk 12
D85
±3d
Wk 24
D169
±7d
Wk 36
D253
±7d
Wk 44
D309
±3d
Wk 48
D337
±3d
Wk 60
D421
±7d
Wk 72
D505
±7d
Wk 84
D589
±7d
EOT 1b
Wk 96
D673
or ET
±7d
Notes
Pharmacokinetic Assessments
See Section 8.5
Blood samples for PK 
assessments
X
X
X
X
X
X
Clinical Efficacy/Health Outcomes
CLASI 
X
X
X
X
X
X
X
X
X
X
X
X
40-joint count
X
X
X
X
X
X
X
X
X
X
X
X
PGA
X
X
X
X
X
X
X
X
X
X
X
X
SDI
X
X
X
X
X
BILAG
X
X
X
X
X
X
X
X
X
X
X
X
SLEDAI-2K
X
X
X
X
X
X
X
X
X
X
X
X
PROMIS Fatigue Short 
Form 7a
X
X
X
X
X
X
X
X
X
X
X
Study Treatment
Randomize using IRT
X
Only subjects on 
placebo in IM011021 
will be rerandomized
Dispense Blinded Study 
Treatment
X
X
X
X
X
X
X
X
X
X
X
X
Study Treatment 
Compliance
X
X
X
X
X
X
X
X
X
X
X
AE = adverse event; BILAG = British Isles Lupus Assessment Group; CK = creatine kinase; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity 
Index; CV = cardiovascular; D = Day; d = days; DNA = deoxyribonucleic acid; dsDNA = double stranded deoxyribonucleic acid; EOS = end of study; EOT = end 
of treatment; ET = early termination; hs-CRP = high-sensitivity C-reactive protein; IGRA = interferon gamma release assay; IRT = interactive response technology; 
PGA = Physician’s Global Assessment; PK = pharmacokinetic; PROMIS = Patient-Reported Outcomes Measurement Information System; 
 
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TYK2 Inhibitor
; SDI = Systemic Lupus Erythematosus Damage Index; SLEDAI 2K = Systemic Lupus Erythematosus Disease Activity Index 2000; TB = tuberculosis; 
UPCR = urine protein/creatinine ratio; Wk = week; WOCBP = women of childbearing potential
a This is the same visit as the EOT visit in IM011021. Any assessments that overlap between IM011074 and IM011021 will not be repeated.
b Unless they withdraw consent for follow-up, subjects who discontinue treatment prior to Week 96 should attend the EOT 1 visit, and then the EOS/follow-up 
visit shown in Table 2 28 days (±3 days) later.
c Events that are ongoing at the time subject signs the informed consent will be reported as AEs. Events reported during IM011021 that have resolved will be 
considered medical history in IM011074.
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TYK2 Inhibitor
Table 2:
On-Treatment Procedural Outline (IM011074): Week 108 through Week 174
Procedure
Wk 108
D757
±7d
Wk 120
D841
±7d 
Wk 134
D939
±7d
Wk 148
D1037
±7d
Wk 162
D1135
±7d
Wk 174
D1219
EOT 2a
or ET
±7d
FU/EOS
Wk 178
D1247
(28d ±3d after 
EOT)
Notes
Safety Assessments
Complete Physical Examination
X
X
X
General, head, eyes, ears, nose, throat, 
neck, CV, lungs, abdominal, 
extremities, neurologic, psychiatric, 
skin, musculoskeletal
Targeted Physical Examination
X
X
X
X
General, eyes, throat, CV, lungs, 
abdominal, extremities, skin, 
musculoskeletal, and others as 
clinically indicated
Body Weight
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
AE Assessment
X
X
X
X
X
X
X
Concomitant Medication Use
X
X
X
X
X
X
X
Corticosteroid Use Assessment
X
X
X
X
X
X
X
Laboratory Tests
Hematology 
X
X
X
X
X
X
X
Chemistry Panel
X
X
X
X
X
X
X
Include CK
Urinalysis
X
X
X
X
X
X
X
UPCR
X
X
X
X
X
X
Coombs Test (direct)
X
X
X
X
X
X
Blood samples for hemolysis 
confirmation
X
X
X
X
X
X
X
Haptoglobin and reticulocyte count
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TYK2 Inhibitor
Table 2:
On-Treatment Procedural Outline (IM011074): Week 108 through Week 174
Procedure
Wk 108
D757
±7d
Wk 120
D841
±7d 
Wk 134
D939
±7d
Wk 148
D1037
±7d
Wk 162
D1135
±7d
Wk 174
D1219
EOT 2a
or ET
±7d
FU/EOS
Wk 178
D1247
(28d ±3d after 
EOT)
Notes
hs-CRP
X
X
X
X
X
X
TB Questionnaire
X
X
IGRA for increased-risk subjects
Pregnancy Test (Urine)
X
X
X
X
X
X
X
WOCBP only
Biomarker Assessments
Serum Complement
X
X
X
X
X
X
X
Anti-dsDNA autoantibodies
X
X
X
X
X
X
X
Clinical Efficacy/Health Outcomes
CLASI 
X
X
X
X
X
X
40-joint count
X
X
X
X
X
X
PGA
X
X
X
X
X
X
SDI
X
X
X
BILAG
X
X
X
X
X
X
SLEDAI-2K
X
X
X
X
X
X
PROMIS Fatigue Short Form 7a
X
X
X
X
X
X
Study Treatment
Dispense Blinded Study 
Treatment
X
X
X
X
X
Study Treatment Compliance
X
X
X
X
X
X
AE = adverse event; BILAG = British Isles Lupus Assessment Group; CK = creatine kinase; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity 
Index; CV = cardiovascular; D = Day; d = days; dsDNA = double-stranded deoxyribonucleic acid; EOS = end of study; EOT = end of treatment; ET = early 
termination; FU = follow-up; hs-CRP = high-sensitivity C-reactive protein; IGRA = interferon gamma release assay; PGA = Physician’s Global Assessment; 
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TYK2 Inhibitor
PROMIS = Patient-Reported Outcomes Measurement Information System; SDI = Systemic Lupus Erythematosus Damage Index; SLEDAI 2K = Systemic Lupus 
Erythematosus Disease Activity Index 2000; TB = tuberculosis; UPCR = urine protein/creatinine ratio; Wk = week; WOCBP = women of childbearing potential
a Unless they withdraw consent for follow-up, subjects who discontinue treatment prior to Week 174 but after Week 96 should attend the EOT 2 visit and the 
EOS/follow-up visit.
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TYK2 Inhibitor
2
INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic progressive autoimmune disease characterized 
by pleiotropic organ/tissue involvement and clinical manifestations which are varied and 
widespread. The most commonly affected body systems are mucocutaneous, musculoskeletal, and 
renal. Progression of the disease is marked by flares requiring therapy modification, and 
uncontrolled SLE leads to end organ damage and death. Current therapies are unsatisfactory and 
include immunosuppressive drugs and corticosteroids, which can temporarily control SLE flares 
and disease progression. However, the utility of these therapies wanes over time, and their use is 
associated with substantial undesirable effects that may outweigh any short-term improvements. 
Tyrosine kinase 2 (TYK2) inhibitors would be expected to demonstrate good efficacy in SLE by 
blocking multiple pathways involved in its pathogenesis and fill an unmet need for novel, 
well-tolerated orally administered therapies.
2.1
Study Rationale
BMS-986165 is the first, potent, oral tyrosine kinase 2 (TYK2) inhibitor with a novel, highly 
selective mechanism of action that has the potential to safely and effectively treat a broad spectrum 
of autoimmune diseases. TYK2 activates intracellular signal transducer and activator of 
transcription (STAT)-dependent transcription and functional responses downstream of receptors 
for critical immune mediators, such as interleukin (IL)-12, IL-23, and Type I and III interferons 
(IFNs).1, 2, 3 These immune and inflammatory signaling pathways are critical in the
pathophysiology 
of 
various 
immune-mediated 
diseases 
including 
psoriasis, 
lupus, 
spondyloarthritis, inflammatory bowel disease, dermatomyositis, and type I interferonopathies.4, 5
BMS-986165 potently inhibits IL-23-, IL-12-, and type I/III IFN-driven responses and has
demonstrated proof of mechanism in mouse models of autoimmunity (psoriasis, colitis, and SLE) 
and in healthy humans.5, 6
Inhibition of TYK2 is expected to provide therapeutic benefit for subjects with SLE for multiple 
reasons: 1) The major pathways in the TYK2 signaling cascade (Type 1 IFN and IL-12/23 and the 
downstream mediators IFNγ and IL-17) have been implicated in SLE disease pathogenesis7; 2) It
is conceivable that TYK2 inhibition may show improved benefits over existing anti-IFN 
monoclonal antibody therapies currently in development because of combined blocking effects on 
both the IL-12/23 and Type 1 IFN pathways.8
A Phase 2 study of BMS-986165 (IM011021) in the treatment of SLE is ongoing. This long-term 
extension (LTE) study will provide additional safety, efficacy, and patient-reported outcome 
(PRO) data of BMS-986165 in subjects participating in IM011021.
2.2
Background
TYK2 is a nonreceptor tyrosine kinase associated with receptors for the p40 containing cytokines 
IL-12 and IL-23, as well as the Type I IFN receptor, and is required for the activation of their 
downstream signaling pathways. TYK2 catalyzes the phosphorylation of the intracellular receptor 
domains and STAT proteins resulting in the activation of STAT-dependent transcription and 
functional responses specific for these cytokines.1, 2, 3 Because TYK2-dependent cytokines (eg, 
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BMS-986165
TYK2 Inhibitor
Type I IFNs, IL-12, IL-23) are distinct from those dependent on closely related Janus kinase (JAK) 
family members JAK1/JAK3 (eg, IL-2, IL-15, IL-7) or JAK2 (eg, erythropoietin, thrombopoietin, 
GM-CSF), a TYK2 inhibitor would be expected to have a highly differentiated profile from 
inhibitors of other JAK family kinases. TYK2-dependent pathways and the cytokine networks they 
modulate (eg, IL-23/IL-17, IFNα) have been implicated in the pathophysiology of multiple 
immune-mediated diseases, including psoriasis, SLE, spondyloarthritides, and Crohn’s disease.
2.2.1
Early Clinical Development
The clinical data available to date supporting the safety, pharmacokinetics (PK), and 
pharmacodynamics (PD) of BMS-986165 are from 5 completed Phase 1 studies in healthy subjects 
(IM011002, IM011015, IM011016, IM011031, and IM011039) and 1 completed Phase 2 study in 
adult subjects with moderate-to-severe plaque psoriasis (IM011011). 
Overall, BMS-986165 has been generally well-tolerated across all studies, and no safety issues 
have been identified to limit the investigation of BMS-986165 in further clinical studies. A detailed 
description of the chemistry, pharmacology, efficacy, and safety of BMS-986165 is provided in 
the Investigator Brochure (IB).
2.3
Benefit/Risk Assessment
The dose selection of BMS-986165 for this study is based on the doses used in the Phase 2 study 
IM011021. At this stage in the development of BMS-986165 for the treatment of patients with 
SLE, assessments of benefit and risk rely on nonclinical data and clinical experience in subjects 
without SLE. The proposed dosing regimens reflect implementation of appropriate safety margins 
and are within the range of doses tested in the first-in-human (FIH) study, the Phase 2 study in 
patients with moderate-to-severe plaque psoriasis (IM011011)9, and within exposure margins 
based on comparisons of systemic exposure and body surface area (BSA).
In a Phase 2 study of subjects with moderate-to-severe plaque psoriasis (Study IM011011), 
BMS-986165 was generally safe and well-tolerated. The most common adverse events (AEs) 
reported by subjects were nasopharyngitis, upper respiratory tract infection, headache, diarrhea, 
and nausea. Most of the AEs reported in the study were mild or moderate in intensity. There were 
8 reversible events of mild to moderate nature of acne that were dose-related (4 at 12 mg once 
daily [QD], 2 at 6 mg twice daily [BID], 1 at 3 mg BID, and 1 at 3 mg every other day). There 
were 7 events of localized oral or nasal herpes simplex lesions that appeared to be dose-related 
(4 at 12 mg QD, 2 at 6 mg BID, and 1 at 3 mg BID). No reports of herpes zoster were noted in this 
study. A total of 6 subjects had creatine kinase (CK) elevations of Grade 3 or higher with no clear 
dose dependence and the CK elevations were temporally associated with increased physical 
activity by the subjects, and thus unlikely to be drug related. No drug-related changes were 
observed in lymphocyte subsets, neutrophils, red blood cells, or cholesterol, which are markers of 
off-target activity on JAK family members JAK1-3, thus supporting the selectivity of 
BMS-986165.
At the maximum concentrations expected in this study (in portal vein or systemic circulation, as 
appropriate), the potential for drug-drug interactions (DDIs) involving cytochrome P450 
(CYP450) enzymes and most transporters is low. BMS-986165 has low turnover in in vitro 
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TYK2 Inhibitor
metabolism studies, and a number of enzymes are involved in the metabolism of the fraction 
metabolized. Additionally, BMS-986165 is not an inhibitor or inducer of CYP450 enzymes at the 
expected clinical concentrations. Therefore, the potential for DDIs resulting from CYP450 
inhibition or induction is low. BMS-986165 is a breast cancer resistance protein (BCRP) inhibitor 
with an in vitro half-maximal inhibitory concentration (IC50) = 0.31 M. However, due to 
overlapping substrate specificity between BCRP and other transporters not affected by 
BMS-986165 at the expected concentrations, the impact of BMS-986165 on the exposures of 
potential comedications that are BCRP substrates, such as rosuvastatin, was also expected to be 
low. This was confirmed in the IM011015 DDI study where co-administration of BMS-986165 
12 mg QD and rosuvastatin 10 mg had no impact on the exposure of rosuvastatin, a BCRP, and 
organic-anion-transporting polypeptide substrate.
Nonclinical data and clinical experience in both healthy subjects, and those with psoriasis in 
combination with the design and doses selected for the current LTE study indicate an overall 
favorable risk/benefit assessment for investigating BMS-986165 as an oral treatment of patients 
with SLE. Detailed information about the known and expected benefits and risks and reasonably 
anticipated AEs of BMS-986165 is provided in the IB.
3
OBJECTIVES AND OUTCOME MEASURES
Table 3:
Objectives and Outcome Measures
Objective
Outcome Measure
Primary
Safety

To characterize the long-term 
safety 
and 
tolerability 
of 
BMS-986165 in subjects with 
SLE

Adverse events and serious adverse events, vital sign 
measurements, and laboratory parameters
Additional
Efficacy

To characterize the long-term 
maintenance 
of 
response 
of 
BMS-986165 in the treatment of 
subjects with SLE

CLASI response

40-joint count for tender, swollen, and tender + swollen 
joints

SRI(4) response

BICLA response

PGA

Corticosteroid use (yes/no)

Corticosteroid dose ≤7.5 mg/day (yes/no)

Flare Analysis
o
Time to first flare
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Table 3:
Objectives and Outcome Measures
Objective
Outcome Measure
o
Number and frequency of flares
o
Flares leading to hospitalization

SDI total score

BILAG response

SLEDAI-2K score

LLDAS response

To characterize patient-reported 
outcomes in subjects with SLE on 
long-term BMS-986165 therapy

PROMIS Fatigue Short Form 7a score
Pharmacokinetic

To 
explore 
long-term 
pharmacokinetics of BMS-986165

Plasma concentrations of BMS-986165
Pharmacodynamic

To 
explore 
long-term 
pharmacodynamics 
of 
BMS-986165

dsDNA, CRP, Complement levels, UPCR
BICLA = BILAG-based Composite Lupus Assessment; BILAG = British Isles Lupus Assessment Group; CLASI = 
Cutaneous Lupus Erythematosus Disease Area and Severity Index; CRP = C-reactive protein; dsDNA = double 
stranded deoxyribonucleic acid; LLDAS = Lupus Low Disease Activity State; PGA = Physician’s Global Assessment; 
PROMIS = Patient-Reported Outcomes Measurement Information System; SDI = Systemic Lupus Erythematosus 
International Collaborating Clinics / American College of Rheumatology Damage Index; SLE = Systemic Lupus 
Erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SRI(4) = Systemic 
Lupus Erythematosus Responder Index; UPCR = urine protein/creatinine ratio
4
STUDY DESIGN
4.1
Overall Design
This will be a double-blind, multi-year, multi-center study to evaluate the long-term safety and 
tolerability of BMS-986165 in subjects who have completed the double-blind treatment period of 
the Phase 2 SLE study IM011021. The blinding to study treatment employed in Study IM011021 
will be maintained in this study. Physical exams, clinical laboratory evaluations, and other 
assessments will be done at select visits during the study. Subjects will be monitored for AEs, and 
blood samples will be collected for biomarker and PK analysis.
Investigator- and subject-administered endpoint assessments will be performed at each scheduled 
clinic visit (Table 1 and Table 2) through the end-of-treatment (EOT) visit (Week 174 or early 
discontinuation); subjects will return to the clinic 28 days after the EOT visit for a safety follow-up 
visit. Unscheduled visits will be allowed throughout the study period as needed for additional 
safety monitoring. Adjustments to subjects’ background SLE therapy will be considered after 
consultation by the investigator with the Medical Monitor(s).
The study design schematic is presented in Figure 1.
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4.1.1
Qualification
At the final treatment visit (Week 48) for the parent SLE study IM011021, the end of study 
procedures will be performed per protocol. Subjects who successfully complete the protocol-
required treatment period will be offered the opportunity to continue to the LTE study. The final 
treatment visit for IM011021 (Week 48) will be the Week 0 visit in IM011074. Refer to Table 1
in the Schedule of Activities (SOA). Prior to enrollment into IM011074, the investigator will 
ensure the following: 
1) subjects remain qualified for continued long-term participation based on the inclusion and 
exclusion criteria from Sections 5.1 and 5.2
2) subjects in IM011021 remain blinded to current treatment prior to enrollment into the LTE
Relevant laboratory data, along with clinical and PRO assessments from the final treatment visit 
(Week 48) in IM011021 will not be repeated at the Week 0 visit. 
Any assessments specific to IM011074 will be performed prior to assignment of IM011074 study 
drug.
4.1.1.1
Treatment Allocation
Qualified subjects from IM011021 will receive blinded BMS-986165 at the same dose as they 
received at the time of study completion. Qualified subjects receiving placebo in IM011021 will 
be randomized 1:1:1 to one of the following active blinded treatment doses:

BMS-986165 12 mg orally (po) QD

BMS-986165 6 mg po BID

BMS-986165 3 mg po BID
Subjects will return to the clinic for assessments every 4 weeks for the first 12 weeks to 
characterize safety and tolerability and efficacy response. Clinic visits will be reduced to every 
12 to 14 weeks thereafter through EOT (Week 174 or early discontinuation). An additional visit 
will occur at Week 44 to ensure an appropriate comparator visit for the Week 48 efficacy 
assessments. Subjects and investigators will remain blinded to the treatment in both the IM011021 
parent study and IM011074. The study design schematic is presented in Figure 1.
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Figure 1:
IM011074 Study Design
BID = twice daily; FU = follow-up; QD = once daily; R = randomize 
Note: For illustrative purposes only. Due to the long treatment period, the number of weeks represented and the 
distances between hashmarks are not to scale.
4.1.2
Data Monitoring Committee 
4.1.2.1
Data Monitoring Committee
An external data monitoring committee (DMC) with multi-disciplinary representation will be used 
during the study to evaluate AEs, laboratory measurements, and safety assessments to ensure the 
ongoing safety of study subjects. An independent reporting statistician not involved in the conduct 
of the study will be designated by PRA to provide the DMC with essential safety data during the 
study.
The DMC responsibilities, authorities, and procedures will be documented and followed according 
to the DMC charter.
4.2
Number of Subjects
The total number of subjects will be based on the number that complete IM011021 and continue 
into IM011074.
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4.3
End of Study Definition
The maximal duration of study participation for individual subjects is expected to be 
approximately 178 weeks.
The start of the study is defined as first visit for first subject completing their parent SLE study 
and enrolling into the IM011074 study. The end of the study is defined as the last visit or scheduled 
procedure shown in the SOA (Section 1.3) for the last subject. Study completion is defined as the 
final date on which data were or are expected to be collected (plus 4 additional weeks for collection 
of potential serious AEs [SAEs]).
4.4
Scientific Rationale for Study Design
The primary purpose of the study is to observe the long-term safety and tolerability of 
BMS-986165 in the treatment of subjects with SLE. All subjects will be permitted to continue their 
background therapies for SLE used in IM011021, and rescue treatments are permitted as needed 
(with a few protocol-specified limitations) to allow subjects to maintain standard disease control 
regardless of the effects of their assigned study treatment. 
4.5
Justification for Dose
Subjects will receive the same dose as in IM011021. Those who were receiving placebo in 
IM011021 will be randomized to one of the 3 active treatments. See Section 4.1.1.1. 
5
STUDY POPULATION
Eligibility criteria for this study have been carefully considered to ensure: 1) safety of the study 
subjects and 2) potential benefit to subjects. It is imperative that subjects fully meet all eligibility 
criteria.
5.1
Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
1) Signed Written Informed Consent
a) Subjects must be willing to participate in the LTE study and must have the ability to sign 
the informed consent form (ICF).
2) Type of Subject and Target Disease Characteristics
a) Completion of Study IM011021 through the protocol-required treatment period, and 
currently receiving blinded study drug. Note: If a subject is not receiving blinded study 
drug due to exceptional circumstances (eg, missed investigational product [IP] due to 
COVID-19 pandemic, delays in study approval, etc), the subject may be allowed to enroll 
with approval from the BMS Clinical Trial Physician or designee.
3) Reproductive Status
a) Women of childbearing potential (WOCBP) must have a negative urine pregnancy test 
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) 
within 24 hours prior to the start of study drug.
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b) Women must not be pregnant, lactating, breastfeeding, or planning pregnancy during the 
study period. 
c) WOCBP must agree to use correctly a highly effective or less than highly effective
method(s) of contraception for the duration of treatment with study drug(s) BMS-986165 
plus 5 half-lives of study drug (3 days) plus 30 days (duration of ovulatory cycle) for a total 
of 33 days post-treatment completion (total of 33 days after last dose of study drug). 
WOCBP who are continuously not heterosexually active are exempt from contraceptive 
requirements, but must still undergo pregnancy testing as described in this protocol
Appendix 4.
d) Male subjects who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception (Appendix 4) for the duration of treatment with study treatment 
BMS-986165. 
e) Azoospermic males are exempt from contraceptive requirements.
Investigators shall counsel WOCBP, and male subjects who are sexually active with WOCBP, on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective or less than highly effective methods of 
contraception (Appendix 4).
5.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study:
1) Medical History and Concurrent Diseases
a) Any disease or medical condition that, in the opinion of the investigator, would make the 
subject unsuitable for this study, would interfere with the interpretation of subject safety or 
study results, or considered unsuitable by the investigator for any other reason. 
2) Findings Related to Possible Tuberculosis (TB) Infection
a) Evidence of active TB
5.3
Lifestyle Restrictions
No restrictions are required. However, general skin care measures that are standard for patients 
with SLE are recommended as follows: use of broad spectrum sunscreen (minimum sun protection 
factor 15 and with inorganic ingredients zinc oxide, titanium dioxide), avoiding sun exposure, 
wearing sun-protective clothing, avoidance of alcohol-based emollients, avoidance of 
over-the-counter anti-acne medications and alcohol-based skin care products, and avoidance of 
perfumed soaps and detergents, and similar measures.
5.3.1
Meals and Dietary Restrictions
Study treatment may be taken without regard to meals.
5.3.2
Caffeine, Alcohol and Tobacco
No restrictions are required.
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5.3.3
Activity
No restrictions are required.
6
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), or placebo 
intended to be administered to a study subject according to the study randomization or treatment 
allocation.
Study treatment includes Investigational [Medicinal] Product (IP/IMP) and can consist of the 
following: BMS-986165 and placebo.
An IP, also known as IMP in some regions, is defined as a pharmaceutical form of an active 
substance or placebo being tested or used as a reference in a clinical study, including products 
already with a marketing authorization but used or assembled (formulated or packaged) differently 
than the authorized form, or used for an unauthorized indication, or when used to gain further 
information about the authorized form.
Other medications used as support or escape medication for preventive, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-IP. 
Table 4 shows the study treatments for Protocol IM011074.
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Table 4:
Study Treatments for IM011074
Product Description / Class 
and Dosage Form
Active Treatment 
Potency
IP/
Non-IMP
Blinded or 
Open-Label
Packaging / Appearance
Storage Conditions
(per label)
BMS-986165 tablet
Placebo tablet to match BMS-
986165 6 mg and 12 mg
3 mg
IP
Blinded
Blister card containing 45 tablets (Active 
3 mg BMS-986165) and placebo tablets to 
match 6 mg and 12 mg (5 tablets per day)
Store at 15 to 25°C;
Protect from light
BMS-986165 tablet
Placebo tablet to match BMS-
986165 3 mg and 12 mg
6 mg
IP
Blinded
Blister card containing 45 tablets (Active 
6 mg BMS-986165) and placebo tablets to 
match 3 mg and 12 mg (5 tablets per day)
Store at 15 to 25°C;
Protect from light
BMS-986165 tablet
Placebo tablet to match BMS-
986165 3 mg and 6 mg
12 mg
IP
Blinded
Blister card containing 45 tablets (Active 
12 mg BMS-986165) and placebo tablets to 
match 3 mg and 6 mg (5 tablets per day)
Store at 15 to 25°C;
Protect from light
IMP = investigational medicinal product; IP = investigational product
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6.1
Treatments Administered
Study treatment will be supplied in blister card kits. Each blister card will contain a nine-day supply 
of 45 tablets arranged into sets where 3 tablets are taken in the morning and 2 tablets are taken in the 
evening, approximately 12 hours apart. For example, a subject in the 12-mg arm would take an active 
12-mg tablet and 2 placebo tablets (to match 3 mg and 6 mg) in the morning, and 2 placebo tablets 
(to match 3 mg and 6 mg) in the evening. Complete dosing information for each treatment group is 
provided in Table 5.
Table 5:
Selection and Timing of Dose
Study 
Treatment
Unit dose strength(s)/
Dosage level(s)
Dosage formulation
Frequency of Administration
Route of 
Administration
12 mg QD 
BMS-986165
12 mg
1 active tablet and 2 placebo tablets in the 
morning, and 2 placebo in the evening
Oral
6 mg BID 
BMS-986165
6 mg
1 active tablet and 2 placebo tablets in the 
morning, and 1 active tablet and 1 placebo tablet 
in the evening
Oral
3 mg BID 
BMS-986165
3 mg
1 active tablet and 2 placebo tablets in the 
morning, and 1 active tablet and 1 placebo tablet 
in the evening
Oral
BID = twice daily; QD = once daily
If a subject forgets a dose, but remembers within 4 hours of the expected dose, the dose should be 
taken. If the missed dose is discovered more than 4 hours after it should have been taken, that dose 
should be not be taken and the next scheduled dose should be taken at the usual time.
6.2
Method of Treatment Assignment
Before the study is initiated, each user (at investigative sites) will receive log-in information and 
directions on how to access the interactive response technology (IRT) system. At the time of the first 
visit in IM011074, immediately after informed consent is obtained and before any study-related 
procedures are performed, the investigative site will access the enrollment option of the IRT system 
for assignment of a subject number for all subjects. The subject number is assigned sequentially by 
the system and will be unique across all sites. All enrolled subjects will be assigned sequential subject 
numbers. The subject number will not be used for any other subject. For continuity purposes, the 
subject number from the parent study will be recorded for each subject enrolled in IM011074.
All subjects who were receiving placebo in the parent study will be centrally randomized in a 1:1:1 
ratio to BMS-986165 12 mg QD, 6 mg BID or 3 mg BID as determined by a computer-generated 
randomization schedule using IRT. All subjects who were on active treatment in the parent study will 
be reallocated to the same treatment regimen in a blinded fashion. A treatment group will be assigned 
by IRT based on the above-described randomization schedule and each subject will be assigned a 
unique randomization number regardless of treatment group in the parent study.
In addition, a kit number will be assigned to the subject corresponding to the treatment assignment. 
The kit will be comprised of blister cards as described in Section 6.1. At subsequent visits, when new 
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treatment kits need to be provided, the investigative site will access IRT to obtain the kit number to 
assign to the subject. 
The investigator will confirm subject eligibility based on criteria in Section 5. 
6.3
Blinding
6.3.1
Maintaining the Blind
Blinded treatment assignments will be managed using IRT. IP supply will be controlled by IRT at 
each visit.
Tablets of each potency of BMS-986165 and its matching placebo are identical in appearance and 
will be supplied in blister cards with each daily dose made up of the appropriate combination of active
and/or placebo capsules/tablets to provide the correct treatment, as shown in Table 5. Investigative 
site staff, Sponsor and designee personnel, and subjects and their families will remain blinded to 
treatment assignments.
6.3.2
Circumstances for Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study and the parent study 
(IM011021). However, in the event of a medical emergency or pregnancy in an individual subject in 
which knowledge of the IP is critical to the subject’s management, the blind for that subject may be 
broken by the investigator. The subject’s safety takes priority over any other considerations in 
determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual subject’s treatment, the investigator should determine that 
the unblinded information is necessary, ie, that it will alter the subject’s immediate management. In
many cases, particularly when the emergency is clearly not related to the IP, the problem may be 
properly managed by assuming that the subject is receiving active product. It is highly desirable that 
the decision to unblind treatment assignment be discussed with the Medical Monitor, but the 
investigator always has ultimate authority for the decision to unblind. The principal investigator 
should only call in for emergency unblinding AFTER the decision to discontinue the subject has been 
made.
In case of an emergency, the investigator has unrestricted access to randomization information via 
IRT and is capable of breaking the blind through the IRT system without prior approval from the 
Sponsor. After the unblinding, the investigator shall notify the Medical Monitor and/or Clinical Trial 
Physician. The method of unblinding for emergency purposes is described in the IRT manual. Subject 
and unblinded treatment information and the reason for the blind being broken must be recorded on 
the appropriate study status page of the electronic case report form (eCRF). After unblinding via IRT, 
the investigator shall notify the Medical Monitor.
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt is made to 
preserve the blind for subject, all other site personnel and the Sponsor/PRA personnel. Any request 
to unblind a subject for nonemergency purposes must be discussed with the Medical Monitor prior to 
unblinding.
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After database lock of the parent study, certain members of the BMS study team will be partially 
unblinded to treatment assignments of some subjects in the current study (ie, those subjects who were 
receiving BMS-986165 in the parent study). An unblinding plan will be created prior to database lock 
of the parent study. Investigators, site personnel, and subjects in both studies will remain blinded to 
treatment assignment.
Designated staff of Bristol-Myers Squibb Company may be unblinded (obtain the randomization 
codes) prior to database lock to facilitate the bioanalytical analysis of pharmacokinetic samples and 
immunogenicity. A bioanalytical scientist in the Bioanalytical Sciences department of Bristol-Myers 
Squibb Research & Development (or a designee in the external central bioanalytical laboratory) will 
be unblinded to (may obtain) the randomized treatment assignments in order to minimize 
bioanalytical analysis of samples.
If a subject is unblinded for any reason, the subject will be discontinued from treatment.
6.4
Dosage Modification
There is no provision for dose-modification of study treatment. If a subject interrupts treatment due 
to an AE, study treatment can be restarted in consultation with the Medical Monitor.
6.5
Preparation/Handling/Storage/Accountability
The IP should be stored in a secure area according to local regulations. It is the responsibility of the 
investigator to ensure that the IP is only dispensed to study subjects. The IP must be dispensed only 
from official study sites by authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by Bristol-Myers Squibb 
(BMS). If concerns regarding the quality or appearance of the study treatment arise, the study 
treatment should not be dispensed and BMS should be contacted immediately.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
IP documentation (whether supplied by BMS or not) must be maintained that includes all processes
required to ensure drug is accurately administered. This includes documentation of drug storage, 
administration and, as applicable, storage temperatures, reconstitution, and use of required processes 
(eg, required diluents, administration sets).

Guidance and information for final disposition of unused study treatment are provided in
Appendix 2.
6.5.1
Retained Samples for Bioavailability/Bioequivalence
Not applicable.
6.6
Treatment Compliance
Study treatment compliance will be periodically monitored using standard drug accountability 
procedures (comparing the number of tablets returned to number dispensed, considering the expected 
regimen and any reported missed doses). Drug accountability will be reviewed by the investigative 
site staff at each visit to confirm treatment compliance. Site staff will discuss any discrepancies with 
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the subject and remind the subject of the importance of compliance with the assigned regimen. A 
real-time monitoring platform may be used.
6.7
Concomitant Therapy
6.7.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications during the study are described below. 
1) Exposure to any investigational drug or placebo outside of the current study is prohibited.
2) Rescue therapy other than prednisone or equivalent is prohibited.
3) Use of intramuscular, intra-articular, intrabursal, and intravenous corticosteroids is prohibited. 
Modified-release corticosteroid formulations are prohibited.
4) Extended-release formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) are prohibited. 
No more than any one type of oral NSAID may be used during the study. NSAID dosing may be 
decreased or discontinued.
5) Use of cyclophosphamide (including ophthalmic) or any biologic agent is prohibited.
6) Live vaccines are prohibited during the study or within 2 months after the last dose. Heat killed, 
or otherwise inactivated or protein vaccines such as influenza, COVID-19, and pneumococcal 
vaccines may be received at any time on study. Any other inactivated vaccines (eg, tetanus, etc) 
should be used according to local guidelines.
The investigator should contact and confirm agreement with the Medical Monitor prior to the 
administration of any concomitant medications.
6.7.2
Permitted Concomitant Medications
Stable doses of concomitant medication for chronic medical conditions are permitted as long as 
neither the medication nor the medical condition meet exclusion criteria as detailed in Section 5.2. 
Dose adjustments of these medications should be avoided during the study unless clinically indicated. 
If a dose adjustment of these medications should occur, they must be recorded on the Concomitant 
Medications eCRF or the Diagnostic and Medical Procedures eCRF. The investigator should instruct 
the subject to notify the study site about any new treatments he/she takes after the start of the study 
treatment. All medications and significant nondrug therapies (including physical therapy and blood 
transfusions) administered after the subject starts study treatment must be listed on the Concomitant 
Medications eCRF or the Diagnostic and Medical Procedures eCRF.
6.7.3
Existing Therapies for Systemic Lupus Erythematosus
All subjects will continue their existing concomitant SLE treatment(s) from IM011021 during the 
IM011074 study. The dose and regimen of background SLE treatments should not change during 
study participation unless approved by the Medical Monitor.
6.7.4
Corticosteroid Treatment
Subjects may continue on existing corticosteroids from the parent study. (Note restrictions in 
Section 6.7.1.) Corticosteroids may be tapered during the study. For increased SLE disease activity 
per investigator judgment, subjects may receive 1 burst of oral corticosteroids within the first 8 weeks 
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of IM011074. Subsequently, 1 burst every 6 months is allowed. If additional bursts are needed, the 
Medical Monitor should be contacted. The burst must not exceed 40 mg/day prednisone or equivalent 
and must return within 7 days to the previous corticosteroids dose used before the burst. 
6.8
Treatment After the End of the Study
At the end of the study, the investigator should ensure that subjects continue to receive appropriate 
standard of care to treat the condition under study. 
At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be eligible 
to receive BMS supplied study treatment. Study treatment will be provided via an extension of the 
study, another rollover study requiring approval by responsible health authority and ethics committee 
or through another mechanism at the discretion of BMS. 
BMS reserves the right to terminate access to BMS supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986165 is 
terminated for other reasons including, but not limited to, lack of efficacy and/or not meeting the 
study objectives; c) the subject can obtain medication from a government sponsored or private health 
program. In all cases BMS will follow local regulations.
7
DISCONTINUATION CRITERIA
7.1
Discontinuation from Study Treatment
Subjects MUST discontinue IP (and non-IP at the discretion of the investigator) for any of the 
following reasons:

Subject requests to stop study treatment. Subjects who request to discontinue study treatment will
remain in the study and must continue to be followed for protocol-specified follow-up procedures. 
The only exception to this is when a subject specifically withdraws consent for any further contact
with him/her or persons previously authorized by subject to provide this information.

Any clinically significant AE, laboratory abnormality, or intercurrent illness, which in the opinion 
of the investigator, indicates that continued participation in the study is not in the best interest of
the subject. If treatment is discontinued due to an AE, the AE eCRF must be completed to show 
that the AE caused discontinuation.

Abnormal liver tests suggestive of drug-induced liver injury (DILI), as defined in Section 8.2.8
or if the investigator believes that it is in the best interest of the subject

The subject develops a malignancy, with the exception of a subject who develops nonmelanoma 
skin cancer who may continue in the study at the discretion of the investigator

Pregnancy, positive pregnancy test, or subject expresses an interest in becoming pregnant (refer 
to Section 8.2.6)

Subject develops active TB during the study or prematurely discontinues treatment for latent 
tuberculosis infection (LTBI), or subject is noncompliant with LTBI therapy (refer to 
Section 8.4.3)

Termination of the study or program by BMS

Unblinding of a subject’s treatment assignment for any reason (emergency or nonemergency)
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
Inability or failure to comply with protocol requirements in the opinion of the investigator

Loss of ability to provide consent without undue influence through imprisonment or involuntary 
incarceration for treatment of either a psychiatric or physical (eg, infectious disease) illness
Refer to the SOA (Section 1.3) for data to be collected at the time of treatment discontinuation and 
follow-up and for any further evaluations that can be completed.
All subjects who discontinue BMS-986165 prior to Week 96 should complete the EOT 1 visit
(Table 1); all subjects who discontinue BMS-986165 after Week 96 but prior to Week 174 should 
complete the EOT 2 visit (Table 2); 28 days (±3 days) after the appropriate EOT visit, all subjects 
should proceed to the 28-day safety follow-up visit with protocol-specified follow-up procedures as 
outlined in Table 2. The only exception to this requirement is when a subject withdraws consent for 
all study procedures including post-treatment study follow-up or loses the ability to consent freely 
(ie, is imprisoned or involuntarily incarcerated for the treatment of either a psychiatric or physical 
illness). Replacement of subjects is not permitted.
If study treatment is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the appropriate 
eCRF page.
7.1.1
Temporary Discontinuation of Study Medication
Temporary study treatment discontinuation is only allowed if the subject develops an AE which, in 
the opinion of the investigator, indicates that it is in the subject’s best interest that the study treatment 
be placed on hold. Study treatment in this situation should be stopped for no longer than 30 days until 
the AE is medically treated and has resolved per principal investigator’s judgment.
Any temporary study treatment discontinuation as well as restart must be documented on the 
corresponding eCRF.
7.1.2
Post-study Treatment Follow-up
Post-study follow-up is of critical importance and is essential to preserving subject safety and the 
integrity of the study. Subjects who discontinue study treatment must continue to be followed for 
collection of outcomes and/or survival follow-up data as required and in line with Section 4 until
death or the conclusion of the study.
Subjects who discontinue study treatment should be encouraged to complete the appropriate EOT
visit (EOT 1 or EOT 2; see Section 7.1) and proceed to the 28-day safety follow-up visit.
If the subject completes the EOT visit, the date of the EOT visit is the subject’s EOT date, and the 
28-day follow-up visit is the subject’s end-of-study (EOS) date. If a subject discontinues treatment 
early, the EOT date is the date of the subject’s last dose, and the EOS date is the date of the 28-day 
safety follow-up EOS visit. If a discontinued subject withdraws consent for further visits or follow-up,
both the EOT and EOS date are the date of the subject’s last dose.
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7.2
Discontinuation from the Study
Subjects who request to discontinue study treatment will remain in the study and must continue to be 
followed for protocol-specified follow-up procedures as specified in Section 1.3. The only exception 
to this is when a subject specifically withdraws consent for any further contact with him/her or 
persons previously authorized by subject to provide this information. 

Subjects should notify the investigator of the decision to withdraw consent from future follow-up 
in writing, whenever possible.

The withdrawal of consent should be explained in detail in the medical records by the investigator 
and entered on the appropriate case report form (CRF) page.

In the event that vital status (whether the subject is alive or dead) is being measured, publicly
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.

If the subject withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent.
7.3
Lost to Follow-Up

All reasonable efforts must be made to locate subjects to determine and report their ongoing 
status. This includes follow-up with persons authorized by the subject.

Lost to follow-up is defined by the inability to reach the subject after a minimum of three
documented phone calls, faxes, or emails as well as lack of response by subject to one registered 
mail letter. All attempts should be documented in the subject’s medical records.

If it is determined that the subject has died, the site will use permissible local methods to obtain 
date and cause of death.

If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’s contact 
information or other public vital status data necessary to complete the follow-up portion of the 
study.

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.

If after all attempts, the subject remains lost to follow-up, then the last known alive date as 
determined by the investigator should be reported and documented in the subject’s medical 
records.
8
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and timing are summarized in the SOA (Section 1.3) and described in 
Section 4.1. 

Protocol waivers or exemptions are not allowed.

All significant safety concerns must be discussed with the Medical Monitor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue treatment.
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
Adherence to the study design requirements, including those specified in the SOA (Section 1.3), 
is essential and required for study conduct.

Procedures conducted as part of the subject’s EOT visit from the parent study and obtained before 
signing of informed consent may be utilized for Week 0 purposes provided the procedure meets 
the protocol-defined criteria and has been performed within the timeframe defined in the SOA
(Section 1.3).

The term “baseline” refers to the baseline visit of the parent study, IM011021.

For several assessments, appropriate training will be provided to investigators at sites. Only those 
individuals trained and certified to perform these assessments will be performing them during the 
study.
8.1
Efficacy Assessments
For new investigators and site staff added since the parent study, protocol-specific training and 
assessments must be successfully completed so that investigators or designees can be qualified to 
perform assessments using the BILAG, CLASI, SLEDAI-2K, and 40-joint count tools. Every effort 
must be made to ensure that the same evaluator(s) complete the assessment for each subject. If the 
evaluator(s) is unable to complete the evaluation, then a qualified individual with overlapping 
experience may perform the evaluation. Documentation of who performed the evaluation is to be 
recorded in source documents. Assessments are to be performed at approximately the same time of 
day throughout the duration of the study. 
Procedures not specified in the protocol that are part of standard care may be performed if they do 
not interfere with study procedures; any data arising from such procedures are not to be reported in 
the eCRF.
8.1.1
Investigator-Administered Assessments
8.1.1.1
British Isles Lupus Assessment Group (BILAG)-2004
The BILAG-2004 rating is based on organ systems (constitutional, mucocutaneous, neuropsychiatric, 
musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each is 
scored by a number of assessments for SLE disease activity, from which an overall grade is derived 
for each organ system. The overall grades are represented as 5 different levels from A to E (A = very 
active, B = moderate disease activity, C = mild stable disease, D = no disease activity but suggests 
the system had previously been affected, and E = no current or previous disease activity). An example 
is provided in Appendix 5.
8.1.1.2
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
The SLEDAI-2K is a global index based on weighted scores for each of 24 clinical findings rated as 
present or absent due to SLE disease activity at the time of the visit or in the last 30 days.10, 11 The 
SLEDAI-2K assigns relative weights to each parameter (see Appendix 6).
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8.1.1.3
Cutaneous Lupus Erythematosus Disease Area and Severity Index
(CLASI)
The CLASI assesses cutaneous disease activity by BSA; points are given for presence of erythema, 
scale, hypertrophy, mucous membrane lesions, recent hair loss, and physician-observed alopecia. For 
the damage assessments, points are given for dyspigmentation, scarring, and scarring alopecia 
(see Appendix 7).
8.1.1.4
40-joint Count
A 40-joint count includes bilateral wrists, elbows, ankles, knees, interphalangeal joints of the thumb, 
individual proximal interphalangeal joints of the hand, second through fifth metacarpophalangeal 
joints of the hand, and individual metatarsophalangeal joints of the feet (which make up the 36-joint 
count).12, 13, 14 To allow the 28-joint count evaluation, bilateral first metacarpophalangeal joints and 
shoulders are also included, bringing the total joint count to 40. Each joint is evaluated based upon 
the presence or absence of tenderness, the presence or absence of swelling, and the presence or 
absence of both tenderness and swelling related to SLE disease activity.
8.1.1.5
SLE Responder Index (SRI[4])
The SRI(4) is a composite endpoint that defines a responder as a patient whose disease course fulfills 
all of the following15:

A ≥4-point reduction from baseline in SLEDAI-2K score10, 11 (Appendix 6)

No new BILAG A (severe disease activity) and not more than 1 new BILAG B (moderate disease 
activity) organ domain grade

No worsening from baseline in the Physician’s Global Assessment of Disease Activity scale by 
more than 0.3 points
8.1.1.6
BILAG-based Composite Lupus Assessment (BICLA)
BICLA response is defined as follows16:

Improvement in all organ systems with BILAG-2004 activity defined as all A scores at baseline
improved to B, C, or D; and all B scores at baseline improved to C or D

No new organ system with activity graded as BILAG A; no more than 1 new organ system with 
activity graded as BILAG B

No increase from baseline in SLEDAI-2K (≤0 points for change from baseline score)

No increase ≥10% in the Physician’s Global Assessment of Disease Activity on a 3-point visual 
analog scale (VAS)

No discontinuation of IP or use of restricted medications beyond the protocol allowed threshold 
before assessment
8.1.1.7
Physician’s Global Assessment (PGA) of Disease Activity
The PGA represents the physician’s overall assessment of average SLE disease severity over the last 
4 weeks assessed using a 3-point VAS (see Appendix 8).
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8.1.1.8
SLE Flares
SLE flares are compared with the previous visit and defined as follows:

Severe flare: Any new or recurrent BILAG-2004 A grade in any body system due to items that 
are scored new or worse

Moderate flare: ≥2 new or recurrent B grades that are due to items scored new or worse

Mild flare: 1 new or recurrent B grade due to items that are scored new or worse; or ≥3 new or 
recurrent C grades due to items that are scored new or worse

No flare: Meeting none of the criteria for mild, moderate, or severe
8.1.1.9
Systemic Lupus Erythematosus International Collaborating Clinics / 
American College of Rheumatology Damage Index (SDI)
The SDI17 assesses damage based on a weighted scoring system for assessments in the following 
areas: ocular, neuropsychiatric, renal, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, 
skin, gonadal, endocrine, and malignancy. Damage is defined as nonreversible change, not related to 
active inflammation, occurring since the onset of lupus, ascertained by clinical assessment and 
present for at least 6 months unless otherwise stated. Repeat episodes must occur at least 6 months 
apart to score 2. The same lesions cannot be scored twice. An example is provided in Appendix 9.
8.1.1.10
Lupus Low Disease Activity State (LLDAS)
LLDAS18, 19 is defined as follows: (1) SLEDAI-2K ≤ 4, with no activity in major organ systems 
(renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or
gastrointestinal activity (measured as maintaining a D or E score in the BILAG Gastrointestinal Body 
System); (2) no new lupus disease activity compared with the previous assessment measured as no 
new or worsening individual BILAG parameters;  (3) Physician’s Global Assessment of Disease 
Activity ≤ 1; (4) a current prednisolone  (or equivalent) dose ≤ 7.5 mg daily; and (5) well tolerated 
standard maintenance doses of immunosuppressive drugs and approved biological agents.
8.1.2
Subject-Reported Assessments
8.1.2.1
Patient-Reported Outcomes Measurement Information System (PROMIS) 
Fatigue
The Patient-Reported Outcomes Measurement Information System (PROMIS™) provides item 
banks that offer the potential for PRO measurement that is efficient (minimizes item number without 
compromising reliability), flexible (enables optional use of interchangeable items), and precise (has 
minimal error in estimate) measurement of commonly-studied PROs.20, 21, 22, 23, 24
In the health outcomes measurement perspective, fatigue is defined as an overwhelming, debilitating, 
and sustained sense of exhaustion that decreases one’s ability to carry out daily activities, including 
the ability to work effectively and to function at one’s usual level in family or social roles. Similar 
subjective feelings, yet fewer behavioral impacts, are associated with lower levels of fatigue. Fatigue 
is divided conceptually into the experience of fatigue (such as its intensity, frequency, and duration), 
and the impact of fatigue upon physical, mental, and social activities.
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The fatigue item bank consists of 95 items assessing the intensity, frequency, and impact of fatigue. 
Most PROMIS items employ response scales with 5 options. A 7-item short form showed strong 
correlation with the full bank, and used the following questions. A 7-day recall is applied because 
there is reasonably high correspondence between real-time symptom reports and 7-day recall of the 
same symptoms.
An example is provided in Appendix 10.
8.2
Adverse Events
The definitions of an AE and SAE can be found in Appendix 3.
All AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject’s legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and reporting events 
that meet the definition of an AE or SAE and remain responsible for following up AEs that are serious, 
considered related to the study treatment or the study, or that caused the subject to discontinue before 
completing the study. 
Contacts for SAE reporting are specified in Appendix 3.
8.2.1
Adverse Events of Interest
Adverse events of interest (AEIs) are AEs for a particular product or class of products that a Sponsor 
may wish to monitor carefully. AEIs may be serious or nonserious. Such events may require further 
investigation to better characterize and understand them. In the BMS-986165 clinical development 
program, certain skin-related AEs (eg, acne) and infection AEs have been identified as potential AEIs; 
however, there has been no definitive assessment on the causal relationship between these events and 
treatment with BMS-986165. Therefore, additional information about certain AEs will be collected 
on the eCRF in order to better characterize and understand them.
8.2.2
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE information should begin at initiation of study treatment until the 
follow-up visit at 28 days after EOT, at the timepoints specified in the SOA (Section 1.3). 
Section 5.6 in the IB represents the Reference Safety Information to determine expectedness of SAEs 
for expedited reporting. Following the subject’s written consent to participate in the study, all SAEs, 
whether related or not related to study drug, must be collected, including those thought to be 
associated with protocol-specified procedures.
All SAEs and AEs related to SARS-CoV-2 infection must be collected from the date of subject’s 
written consent until 30 days after the final dose of the study drug or subject’s participation in the 
study if the last scheduled visit occurs at a later time. Monitoring for SAEs will occur at every study 
visit. 

The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure. Medical occurrences that begin before 
the start of study treatment but after obtaining informed consent will be recorded on the 
appropriate section of the CRF.
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
All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated in 
Appendix 3.

The investigator will submit any updated SAE data to the Sponsor within 24 hours of this being 
available.
Investigators are not obligated to actively seek AEs or SAEs in former study subjects. However, if 
the investigator learns of any SAE, including a death, at any time after a subject has been discharged 
from the study, and he/she considers the event reasonably related to the study treatment or study 
participation, the investigator must promptly notify the Sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for completing 
and reporting/transmitting SAE reports are provided in Appendix 3.
8.2.3
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a subject. (In order to prevent reporting bias, subjects should not be questioned 
regarding the specific occurrence of one or more AEs).
8.2.4
Follow-up of AEs and SAEs

Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of study 
treatment and for those present at the end of study treatment as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of the 
CRF. Completion of supplemental CRFs may be requested for certain AEs such as skin 
reactionsand infections, and/or laboratory abnormalities that are reported/identified during the 
course of the study.

After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs and AES related to COVID-19 will be followed until 
resolution, until the condition stabilizes, until the event is otherwise explained, or until the subject 
is lost to follow-up (as defined in Section 7.3).
Further information on follow-up procedures is given in Appendix 3.
8.2.5
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal obligations 
and ethical responsibilities towards the safety of subjects and the safety of a product under clinical 
investigation are met.

An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with the 
IB and will notify the IRB/IEC, if appropriate according to local requirements.
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The Sponsor or a designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws including European Directive 2001/20/EC and Food and Drug 
Administration (FDA) Code of Federal Regulations 21 CFR Parts 312 and 320. A SUSAR 
(Suspected, Unexpected Serious Adverse Reaction) is a subset of SAEs and will be reported to the 
appropriate regulatory authorities and investigators following local and global guidelines and 
requirements.
8.2.6
Pregnancy
In the event a subject becomes pregnant during the trial, the study treatment must be discontinued 
immediately. If the subject becomes pregnant while on treatment or within 3 days of discontinuing 
study treatment, the investigator must immediately notify the PRA Drug Safety department of this 
event and complete and forward a Pregnancy Surveillance Form to PRA Drug Safety within 24 hours 
of awareness of the event and in accordance with SAE reporting procedures described in Appendix 
3. The investigator must also notify the Medical Monitor or designee of this event within 24 hours of 
awareness of pregnancy. 
The pregnant subject will need to be followed up until the conclusion of the pregnancy for pregnancy 
outcomes. The safety data of the subject will continue to be collected under the same rules as 
instructed in Section 7.1.
Any pregnancy that occurs in a female partner of a male study subject should be reported to PRA 
Drug Safety. In order for the Sponsor or designee to collect any pregnancy surveillance information 
from the female partner, the female partner must sign an ICF for disclosure of this information. 
Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
8.2.7
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF page 
or SAE electronic Report Form, as appropriate. Paper forms are only intended as a back-up option 
when the electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the subject to have study treatment 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia vs low hemoglobin value).
8.2.8
Potential Drug-Induced Liver Injury (DILI)
All occurrences of potential DILIs, meeting the defined criteria, must be reported as SAEs (see 
Section 8.2 and Appendix 3 for reporting details). Wherever possible, timely confirmation of initial 
liver-related laboratory abnormalities should occur prior to the reporting of a potential DILI event.
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Potential DILI is defined as: 
1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation >3 times upper 
limit of normal (ULN)
AND
2) Total bilirubin >2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase),
AND
3) No other immediately apparent possible causes of liver function test elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, preexisting chronic or acute liver 
disease, or the administration of other drug(s) known to be hepatotoxic.
8.2.9
Other Safety Considerations
Any significant worsening of a preexisting medical condition noted during interim or final physical 
examination, x-ray filming, or any other potential safety assessment required or not required by 
protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
8.3
Overdose
For this study, taking > 24 mg of study drug within a 24-hour time period will be considered an 
overdose. If a subject has frequent or longer durations of taking more than the specified doses, the 
investigator should discuss the situation with the Medical Monitor.
In the event of an overdose the investigator should:
1) Contact the Medical Monitor immediately
2) Closely monitor the subject for AEs/SAEs and laboratory abnormalities 
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 subject.
8.4
Safety
Planned time points for all safety assessments are listed in the SOA (Section 1.3).
8.4.1
Physical Examinations
A complete physical examination will include general appearance, vital signs, eyes, ears, nose, 
mouth, throat, neck, respiratory, cardiovascular, respiratory, gastrointestinal/abdomen, lymphatic, 
musculoskeletal, skin, psychiatric, and neurologic exams. A targeted physical examination will 
include any organ system associated with an AE or a laboratory abnormality.
8.4.2
Vital Signs
Refer to SOA (Section 1.3).
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8.4.3
Tuberculosis Assessment 
A subject must not have active signs or symptoms of TB, as judged by the investigator, to be eligible 
for the study.
In addition to a complete PE and medical history to evaluate exposure to TB, all subjects will 
complete a TB questionnaire annually (refer to Appendix 11). If subjects are at increased risk for TB, 
they may still roll over into the study and begin study treatment and procedures at Week 0 
(Section 1.3); however, they will have an Interferon Gamma Release Assay (IGRA) at the Week 0
visit, and the result should be obtained promptly. If IGRA results are:
a) Negative; no further action is needed
b) Positive; subject must initiate prophylaxis treatment per local guidelines. IP will be held until 
subject has been on prophylaxis treatment for 30 days.
c) Indeterminate; an IGRA retest will be allowed. Subject must initiate prophylaxis treatment per 
local guidelines. IP will be held until subject has been on prophylaxis treatment for 30 days.
8.4.4
Clinical Safety Laboratory Assessments

A central laboratory will perform assessments of safety laboratory assessments (except pregnancy 
tests) and provide reference ranges and laboratory reports. Investigators must document their 
review of each laboratory safety report. Any laboratory test result that the investigator considers 
clinically relevant is to be recorded on the appropriate AE page of the eCRF (Section 8.2.7) unless 
lupus-related and recorded on the lupus assessments. Additional safety assessments may be 
performed at local laboratories at the investigator’s discretion. The laboratory parameters to be 
assessed are as follows:

Hematology: hemoglobin, hematocrit, total leukocyte count (including differential), 
platelet 
count, red blood cell count, and manual differential (separate smear)

Chemistry: AST, ALT, gamma-glutamyltransferase, hs-CRP, total bilirubin, direct bilirubin, 
alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, glucose, 
total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, magnesium, CK, 
creatinine clearance (Week 0 only)

Urinalysis: protein, glucose, blood, leukocyte esterase, specific gravity, pH; microscopic 
examination of the sediment if blood, protein, or leukocyte esterase are positive on dipstick; spot 
urine will be assessed for urine protein and urine creatinine

IGRA
Samples for confirmation of hemolysis (using haptoglobin and reticulocyte count) for the BILAG 
will be drawn at assessment visits and stored at the central laboratory; the samples will only be 
analyzed if there is clinical suspicion on the part of the investigator. In addition, urine pregnancy 
testing will be performed for WOCBP.
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8.5
Pharmacokinetics
The PK of BMS-986165 and metabolites (if applicable) will be derived from plasma concentration 
vs time data. The PK parameter to be assessed will be trough observed plasma concentration 
(Ctrough). 
Plasma samples will be analyzed for BMS-986165 by a validated assay. Individual subject PK 
parameter values will be derived by noncompartmental methods by a validated PK analysis program. 
Actual times will be used for the analyses. Population PK modelling might be conducted and 
documented in a separate report.
In addition, plasma samples will be archived for potential metabolite analysis, if the need arises and 
to the extent possible. Detailed instructions for PK blood collection, labeling, processing, storage, 
and shipping will be provided to the site in the Study Reference Manual.
8.5.1
Sampling Schedule
The sampling schedule for the assessment of PK is provided in Table 6. Predose samples must be 
drawn before the dose on visit days. The timing of other procedures at a given visit can be adjusted 
so that PK sampling can be performed at the scheduled time. If possible, PK samples should be 
collected for subjects who discontinue treatment due to an AE.
Table 6:
Pharmacokinetic Sampling Schedule for BMS-986165
Study Visit of Sample 
Collection
Event
Time
(Relative to Dose)
Hour: Min
Blood Sample for PK
Notes
Week 0
predose
00:00
X
Week 4
predose
00:00
X
Week 8
predose
00:00
X
Week 24
predose
00:00
X
Week 48
predose
00:00
X
Week 96
predose
00:00
X
min = minute; PK = pharmacokinetic
Note: Predose samples must be drawn before the morning dose of study treatment on the visit day. ie, study treatment 
will be taken at the site on those days.
8.5.2
Sampling Windows
It is expected that every effort is made to collect PK samples at the times indicated. Predose 
samples must be drawn before the morning dose on the visit day. 
All samples should be collected using the timepoint labels provided even if they are outside of the 
suggested window. Actual sample times must be recorded. Any missed PK sample collections must 
be noted in the source documents.
8.6
Exploratory Biomarker Assessments 
 
 
 
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8.6.2
Additional Research Collection
This protocol will include residual sample storage for additional research.
For All US sites:
Additional research is required for all study subjects, except where prohibited by IRBs/ethics 
committees, or academic/institutional requirements. Where one or more of these exceptions occurs, 
participation in the additional research should be encouraged, but will not be a condition of overall 
study participation. 

If the IRB/ethics committees and site agree to the mandatory additional research retention and/or 
collection, then the study subject must agree to the mandatory additional research as a requirement 
for inclusion in the study.

If optional participation is permitted and approved, then the study subjects may opt out of the 
additional research retention and/or collection.
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For non-US Sites
Additional research is optional for all study subjects, except where retention and/or collection is 
prohibited by local laws or regulations, ethics committees, or institutional requirements. 
This collection for additional research is intended to expand the translational Research and 
Development (R&D) capability at BMS and will support as yet undefined research aims that will 
advance our understanding of disease and options for treatment. It may also be used to support health 
authority requests for analysis and advancement of pharmacodiagnostic development to better target 
drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring 
disease pathways, progression and response to treatment etc.
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study Sponsor’s senior leaders in R&D (or designee) to ensure the research supports 
appropriate and well-defined scientific research activities. 

Residual PK
 
 (see Table 7) 
will be retained for additional research purposes.
The manager of these samples will ensure they are properly used throughout their usable life and will 
destroy the samples at the end of the scheduled storage period, no longer than 15 years after the end 
of the study or the maximum allowed by applicable law.
Transfers of samples by research Sponsor to third parties will be subject to the recipient’s agreement 
to establish similar storage procedures.
Samples will be stored in a coded fashion and no researcher will have access to the key. The key is 
securely held by the investigator at the clinical site, so there is no direct ability for a researcher to 
connect a sample to a specific individual.
Table 7:
Residual Sample Retention for Additional Research Schedule 
Sample Type
Timepoints for which residual samples will be retained
PK
All
 PK = pharmacokinetic; 
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8.7
Health Economics OR Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters will not be 
evaluated in this study.
9
STATISTICAL CONSIDERATIONS
9.1
Sample Size Determination
As this LTE study is for observational purposes only, no formal calculations of sample size and power 
determination were made. All qualified subjects who complete the final treatment visit from the
parent study will be eligible to participate. If a 
 response rate is observed in a treatment group 
with a sample size of 
, then one can be 95% confident that the interval 
 contains the 
true response rate. Assuming 360 subjects enrolling from IM011021, there will be approximately a 
 chance of observing an AE that occurs in at least 
 of the population.
9.2
Populations for Analyses
For purposes of analysis, the following analysis sets will be used in this trial:
Enrolled Population:  All subjects who sign informed consent for entry into IM011074
As-treated Population:  All subjects who took at least one dose of study treatment in IM011074. 
The treatment group ‘as-treated’ will be the same as the treatment group the subjects were assigned 
to in this study, except in the following cases:

If a subject took the same incorrect treatment throughout this study, then the subject will be 
analyzed based on the treatment received.

If a subject took study drug from more than one treatment group, and none of the administrations 
were consistent with the assigned treatment group, then the subject will be analyzed based on the 
first treatment taken.
Biomarker Population: All subjects who receive at least one dose of study treatment in IM011074 
and have at least 1 post-treatment biomarker measurement
Pharmacokinetic (PK) Population:  All subjects who receive at least one dose of study treatment 
in IM011074 and have any available concentration-time data
9.3
Endpoints 
9.3.1
Safety Assessments – Primary Endpoint
The primary objective of this LTE study is to characterize the long-term safety and tolerability of 
BMS-986165 in subjects with SLE. The following assessments will be summarized for the evaluation 
of this objective:

AEs, SAEs, AEs leading to study discontinuation 

Change from baseline in vital signs over time

Change from baseline in laboratory measurements over time
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9.3.2
Secondary Endpoints
Not applicable
9.3.3
Additional Endpoints
The following endpoints will be measured throughout the study: 
-
Proportion of subjects with a CLASI activity score ≥ 10 at baseline and who achieve a CLASI 
response, defined as a decrease of ≥ 50% from baseline CLASI activity score 
-
Proportion of subjects with a CLASI activity score at baseline < 10 who maintain a score of 
< 10 at each visit
-
Change from baseline in CLASI activity score
-
Change from baseline in the 40-joint count for tender, swollen and tender + swollen joints 
-
Proportion of subjects who meet SRI(4) response criteria. SRI(4) response is defined in 
Section 8.1.1.5.
-
Proportion of subjects who achieve BICLA response. BICLA response is defined in 
Section 8.1.1.6.
-
Change from baseline in PGA of Disease Activity 
-
Proportion of subjects using corticosteroids at each visit during the Blinded LTE Study Period
-
Proportion of subjects receiving daily corticosteroid dose ≤7.5 mg/day assess at each visit 
during the Blinded LTE Study Period
-
SLE Flare Analysis:
o
Time to subjects first flare
o
Proportion of subjects with flares and severity 
o
Total number of flares per subject 
o
Frequency of flares
o
Proportion of flares leading to hospitalization
-
Changes in SDI Score
-
Proportion of subjects with BILAG-2004 response
-
Change from baseline in BILAG-2004 score
-
Change from baseline in SLEDAI-2K score
-
Proportion of subjects with LLDAS response
-
PROs:
o
Change from baseline in PROMIS Fatigue Short Form 7a Score
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9.3.4
PK Endpoints
Plasma concentration values
9.3.5
PD Endpoints
Exploratory Biomarkers
9.4
Efficacy Analyses
As this study is for observational purposes, no statistical tests for treatment comparisons will be 
conducted. Categorical data will be summarized as frequency counts and percentages. Continuous 
data will be summarized using number of subjects (n), mean, standard deviation, median, minimum, 
and maximum unless otherwise specified. Efficacy variables will be summarized for all visits in 
which the variable is assessed. Complete details of the planned analyses will be documented in the 
statistical analysis plan and finalized before database lock. Summaries will be provided for the ‘as-
treated’ population. 
Summaries of outcome measures (or endpoints) will be presented for the following groups:

BMS-986165 3 mg BID (treatment from previous study) → BMS-986165 3 mg BID

BMS-986165 6 mg BID (treatment from previous study) → BMS-986165 6 mg BID

BMS-986165 12 mg QD (treatment from previous study) → BMS-986165 12 mg QD

Placebo BID (treatment from previous study) → BMS-986165 3 mg BID

Placebo BID (treatment from previous study) → BMS-986165 6 mg BID

Placebo BID (treatment from previous study) → BMS-986165 12 mg QD
9.5
Safety Analyses
Safety data will be analyzed for AEs, SAEs, laboratory analytes, and vital signs. Safety will be 
summarized using the ‘as-treated’ population. Categorical data will be summarized as frequency 
counts and percentages. Continuous data will be summarized using n, mean, standard deviation, 
median, minimum, and maximum unless otherwise specified.
Safety summaries will be presented according to the following groups:

BMS-986165 3 mg BID (treatment from previous study) → BMS-986165 3 mg BID

BMS-986165 6 mg BID (treatment from previous study) → BMS-986165 6 mg BID

BMS-986165 12 mg QD (treatment from previous study) → BMS-986165 12 mg QD

Placebo BID (treatment from previous study) → BMS-986165 3 mg BID

Placebo BID (treatment from previous study) → BMS-986165 6 mg BID

Placebo BID (treatment from previous study) → BMS-986165 12 mg QD
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9.5.1
Adverse Events
Adverse events will be recorded at the time of the last study visit in the parent study. Events that are 
ongoing at the time subject signs the informed consent will be reported as AEs. Events reported 
during IM011021 that have resolved will be considered medical history in IM011074. 
Treatment-emergent adverse events (TEAEs) are events that occur after the first dose of study drug 
is given in the LTE study. Events that were ongoing during the parent study and worsen once study 
drug is initiated in IM011074 will also be considered treatment-emergent. All AEs will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA) and presented by system organ 
class and preferred term. Serious AEs and deaths, AEs leading to study treatment discontinuation, 
AEs by maximum severity, and AEs by relationship will also be summarized by the MedDRA system 
organ class and preferred term. All TEAEs will also be summarized by preferred term sorted by 
decreasing frequency. 
9.5.2
Vital Signs, and Physical Examinations
Vital signs will be summarized as raw change from baseline, and change from maximum postbaseline 
value. Incidence of abnormal physical examination findings will also be summarized.
9.5.3
Clinical Laboratory Tests
Laboratory analytes will be summarized as raw change from baseline, and change from maximum 
postbaseline value. Incidence of abnormal, high, or low values will be summarized. Shift tables will 
also be provided.
9.6
Other Analyses 
Other analysis summaries will be presented by treatment groups similar as defined in Section 9.5.
9.6.1
Demographics and Baseline Data
Demographics and baseline data obtained during the screening visit of study IM011021 will be 
summarized for subjects entering the LTE and will be summarized by randomized treatment for each 
applicable analysis population. Categorical data will be summarized as frequency counts and 
percentages. Continuous data will be summarized using n, mean, standard deviation, median, 
minimum, and maximum unless otherwise specified.
9.6.2
Prior and Concomitant Medications
Prior and concomitant medications, categorized by medication group and subgroup according to the 
World Health Organization (WHO) Drug Dictionary, will be summarized by treatment for the ‘as-
treated’ population. Medications with an end date prior to the first dose of LTE study drug will be 
considered prior medications.
9.6.3
Pharmacokinetics
Ctrough will be summarized by dose and timepoint for the PK population. If warranted, analysis of 
PK and exposure-response relationships of BMS-986165 will be conducted using a population 
approach as appropriate and reported separately from the CSR.
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9.6.4
Exploratory Biomarkers
Selected biomarkers will be summarized by treatment and time point for the biomarker population. 
Summaries will be provided for raw, change from baseline, and percent change from baseline.
9.7
Interim Analyses
No interim analysis is currently planned.
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REFERENCES
1.
Watford WT, Hissong BD, Bream JH, et al. Signaling by IL-12 and IL-23 and the 
immunoregulatory roles of STAT4. Immunol Rev 2004;202:139-56.
2.
Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine kinase 2-mediated signal 
transduction in T lymphocytes is blocked by pharmacological stabilization of its pseudokinase 
domain. J Biol Chem 2015;290(17):11061-74.
3.
Shaw MH, Boyartchuk V, Wong S, et al. A natural mutation in the Tyk2 pseudokinase domain 
underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. Proc Natl 
Acad Sci U S A 2003;100(20):11594-9.
4.
Volpe E, Servant N, Zollinger R, et al. A critical function for transforming growth factor-beta, 
interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 
responses. Nat Immunol 2008;9(6):650-7.
5.
Geremia A, Arancibia-Carcamo CV, Fleming MP, et al. IL-23-responsive innate lymphoid 
cells are increased in inflammatory bowel disease. J Exp Med 2011;208(6):1127-33.
6.
Strober BE, Crowley JJ, Yamauchi PS, et al. Efficacy and safety results from a Phase III, 
randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept 
and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 
2011;165(3):661-8.
7.
Characterization of Tyk2 inhibitor, BMS-986165, in biochemical and human immune cell 
assays (Study IMM0043). Bristol-Myers Squibb Company; 2015. Document Control No. 
930087619.
8.
Brkic Z, Corneth OB, van Helden-Meeuwsen CG, et al. T-helper 17 cell cytokines and 
interferon type I: partners in crime in systemic lupus erythematosus? Arthritis Res Ther 
2014;16(2):R62.
9.
Papp K, Gordon K, Thaci D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in 
psoriasis. N Engl J Med 2018;379(14):1313-21.
10.
Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 
2000. J Rheumatol 2002;29(2):288-91.
11.
Touma Z, Urowitz MB, Gladman DD. SLEDAI-2K for a 30-day window. Lupus 
2010;19(1):49-51.
12.
Egger MJ, Huth DA, Ward JR, et al. Reduced joint count indices in the evaluation of 
rheumatoid arthritis. Arthritis Rheum 1985;28(6):613-9.
13.
Sokka T, Pincus T. Quantitative joint assessment in rheumatoid arthritis. Clin Exp Rheumatol 
2005;23(5 Suppl 39):S58-62.
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14.
Fuchs HA, Brooks RH, Callahan LF, et al. A simplified twenty-eight-joint quantitative 
articular index in rheumatoid arthritis. Arthritis Rheum 1989;32(5):531-7.
15.
Furie R, Petri MA, Strand V, et al. Clinical, laboratory and health-related quality of life 
correlates of Systemic Lupus Erythematosus Responder Index response: a post hoc analysis 
of the phase 3 belimumab trials. Lupus Sci Med 2014;1(1):e000031.
16.
Wallace DJ, Kalunian K, Petri MA, et al. Efficacy and safety of epratuzumab in patients with 
moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, 
randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis 
2014;73(1):183-90.
17.
Gladman DD, Urowitz MB, Goldsmith CH, et al. The reliability of the Systemic Lupus 
International Collaborating Clinics/American College of Rheumatology Damage Index in 
patients with systemic lupus erythematosus. Arthritis Rheum 1997;40(5):809-13.
18.
Franklyn K, Lau CS, Navarra SV, et al. Definition and initial validation of a Lupus Low 
Disease Activity State (LLDAS). Ann Rheum Dis 2016;75(9):1615-21.
19.
Golder V, Kandane-Rathnayake R, Hoi AY, et al. Frequency and predictors of the lupus low 
disease activity state in a multi-national and multi-ethnic cohort. Arthritis Res Ther 
2016;18(1):260.
20.
Bartlett SJ, Orbai AM, Duncan T, et al. Reliability and validity of selected PROMIS measures 
in people with rheumatoid arthritis. PLoS One 2015;10(9):e0138543.
21.
Cella D, Riley W, Stone A, et al. The Patient-Reported Outcomes Measurement Information 
System (PROMIS) developed and tested its first wave of adult self-reported health outcome 
item banks: 2005-2008. J Clin Epidemiol 2010;63(11):1179-94.
22.
Garcia SF, Cella D, Clauser SB, et al. Standardizing patient-reported outcomes assessment in 
cancer clinical trials: a patient-reported outcomes measurement information system initiative. 
J Clin Oncol 2007;25(32):5106-12.
23.
Lai JS, Cella D, Yanez B, et al. Linking fatigue measures on a common reporting metric. J 
Pain Symptom Manage 2014;48(4):639-48.
24.
Katz P, Margaretten M, Gregorich S, et al. Physical activity to reduce fatigue in rheumatoid 
arthritis: a randomized controlled trial. Arthritis Care Res (Hoboken) 2018;70(1):1-10.
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
 
AE
adverse event
AEI
adverse event of interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC(TAU)
area under the concentration-time curve for 1 
dosing interval
BCRP
breast cancer resistance protein
BICLA
BILAG-based Composite Lupus Assessment
BID
twice daily
BILAG
British Isles Lupus Assessment Group
BMS
Bristol-Myers Squibb
BSA
body surface area
Cavg, ss
average concentration at steady state
CFR
Code of Federal Regulations
CK
creatine kinase
CLASI
Cutaneous Lupus Erythematosus Disease 
Area and Severity Index
CRF
case report form
CRP
C-reactive protein
CSR
clinical study report
Ctrough
trough observed plasma concentration 
CV
cardiovascular
CXR
chest x-ray
CYP450
cytochrome P450
DDI
drug-drug interaction
DILI
drug-induced liver injury
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Term
Definition
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
dsDNA
double stranded DNA
eCRF
electronic case report form
FDA
Food and Drug Administration
FIH
first-in-human
FSH
follicle-stimulating hormone
hCG
human chorionic gonadotropin
hs-CRP
high-sensitivity C-reactive protein
IB
Investigator Brochure
IBD
inflammatory bowel disease
IC50
half-maximal inhibitory concentration
ICF
informed consent form
IEC
Independent Ethics Committee
IFN
interferon
IFN
interferon gamma
IGRA
interferon gamma release assay
IL
interleukin
IMP
investigational medicinal product
IP
investigational product 
IRB
Institutional Review Board
IRT
interactive response technology
JAK
Janus kinase
LLDAS
Lupus Low Disease Activity State
LTBI
latent tuberculosis infection
LTE
long-term extension
MedDRA
Medical Dictionary for Regulatory Activities
NSAID
nonsteroidal anti-inflammatory drug
PD
pharmacodynamics
PGA
Physician Global Assessment
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Term
Definition
PK
pharmacokinetics
po
orally
PRO
patient-reported outcome
PROMIS
Patient-Reported Outcomes Measurement 
Information System
QD 
once daily
R&D
Research and Development
 
SAE
serious adverse event
SDI
Systemic Lupus Erythematosus International 
Collaborating Clinics / American College of 
Rheumatology Damage Index
SLE
Systemic Lupus Erythematosus
SLEDAI
Systemic Lupus Erythematosus Disease 
Activity Index
SOA
Schedule of Activities
SRI(4)
SLE Responder Index
STAT
signal transducer and activator of 
transcription
SUSAR
Suspected, Unexpected Serious Adverse 
Reaction
TB
tuberculosis
TEAE
treatment-emergent adverse event
Tmax
time of maximum observed plasma 
concentration
TYK2
tyrosine kinase 2
ULN
upper limit of normal
UPCR
urine protein/creatinine ratio
VAS
visual analog scale
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
Regulatory and Ethical Considerations
Good Clinical Practice
This study will be conducted in accordance with:

Good Clinical Practice (GCP) 

as defined by the International Council for Harmonisation (ICH)

in accordance with the ethical principles underlying European Union Directive 2001/20/EC

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 

applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive approval/favorable opinion by Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to Sponsor or designee immediately. A serious 
breach is a breach of the conditions and principles of GCP in connection with the study or the 
protocol, which is likely to affect, to a significant degree, the safety or physical or mental integrity 
of the subjects of the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
Institutional Review Board/Independent Ethics Committee
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The investigator 
or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure or product 
labeling information to be provided to subjects and any updates. 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
Compliance with the Protocol and Protocol Revisions
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
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If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as soon 
as possible to:

IRB/IEC

Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the subject: 
(1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
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 health 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.
Informed Consent Process
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives (as 
per country guidelines) are clearly and fully informed about the purpose, potential risks, and other 
critical issues regarding clinical studies in which the subject volunteers to participate. 
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form (ICF), which will include all elements required by ICH, GCP, and 
applicable regulatory requirements. The sample ICF will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:

Provide a copy of the consent form and written information about the study in the language in 
which the subject is most proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 

Allow time necessary for subject or subject’s legally acceptable representative to inquire about 
the details of the study.
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
Obtain an informed consent signed and personally dated by the subject or the subject’s legally 
acceptable representative and by the person who conducted the informed consent discussion. 

Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF and any other 
information to be provided to the subjects, prior to the beginning of the study, and after any 
revisions are completed for new information.
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or her 
informed consent during the study, consent must additionally be obtained from the subject.
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject’s consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject’s legally acceptable representative or legal guardian, 
of all pertinent aspects of the study and of any new information relevant to the subject’s willingness 
to continue participation in the study. This communication should be documented. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects’ signed ICF and, in 
the US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
For minors, according to local legislation, one or both parents or a legally acceptable representative 
must be informed of the study procedures and must sign the ICF approved for the study prior to 
clinical study participation. The explicit wish of a minor, who is capable of forming an opinion 
and assessing this information to refuse participation in, or to be withdrawn from, the clinical study 
at any time should be considered by the investigator. 
Minors who are judged to be of an age of reason must also give their written assent.
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to refuse 
participation in, or to be withdrawn from, the clinical study at any time should be considered by 
the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
Source Documents
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
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or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
AE tracking/reporting, protocol-required assessments, and/or drug accountability records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
Study Treatment Records
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a health authority.
If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

amount received and placed in storage 
area

amount currently in storage area

label identification number or batch 
number

amount dispensed to and returned by each 
subject, including unique subject 
identifiers

amount transferred to another area/site for 
dispensing or storage

nonstudy disposition (eg, lost, wasted) 

amount destroyed at study site, if 
applicable

amount returned to BMS

retain samples for 
bioavailability/bioequivalence, if 
applicable 

dates and initials of person responsible for 
Investigational Product 
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If
Then
dispensing/accountability, as per the 
Delegation of Authority Form.
Sourced by site, and not supplied by BMS or 
its vendors (examples include IP sourced 
from the sites stock or commercial supply, or 
a specialty pharmacy)
The investigator or designee accepts 
responsibility for documenting traceability 
and study treatment integrity in accordance 
with requirements applicable under law and 
the SOPs/standards of the sourcing pharmacy.   
These records should include:

label identification number or batch 
number 

amount dispensed to and returned by each 
subject, including unique subject 
identifiers

dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the 
Delegation of Authority Form.
BMS or designee will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and paper Pregnancy Surveillance Form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used.
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
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The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature is completed electronically through the 
electronic data capture tool. The investigator must retain a copy of the CRFs including records of 
the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the electronic data capture tool using the unique user account 
provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals.
Monitoring
Sponsor or designee representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents:
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee. 
Records Retention
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
Return of Study Treatment
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially-used study treatment containers, vials and syringes may be destroyed on site. 
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If
Then
Study treatments supplied by BMS (including 
its vendors)
Any unused study treatments supplied by 
BMS can only be destroyed after being 
inspected and reconciled by the responsible 
Study Monitor unless study treatments 
containers must be immediately destroyed as 
required for safety, or to meet local 
regulations (eg, cytotoxics or biologics).
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or commercial supply, or a specialty 
pharmacy)
It is the investigator’s or designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of nonstudy 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
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Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the CSR.
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria:

External Principal Investigator designated at protocol development

National Coordinating Investigator 

Study Steering Committee chair or their designee

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Regional representation (eg, among top quartile of enrollers from a specified region or country)

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing study site or investigator participation in the 
study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTA.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject-administered study drug and 
that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study drug, whether or not 
considered related to the study drug.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, electrocardiograms, radiological scans, vital 
signs measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Note that 
abnormal lab tests or other safety assessments should only be reported as AEs if the 
final diagnosis is not available. Once the final diagnosis is known, the reported term 
should be updated to be the diagnosis. 

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose as a verbatim term (as reported by 
the investigator), should not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae and should specify "intentional overdose" as the 
verbatim term.
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
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DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
SERIOUS ADVERSE EVENTS
Serious Adverse Event Definition: Any untoward medical occurrence that, at any dose:
Results in death
Is life-threatening (defined as an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe)
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see note 
below)
Note: The following hospitalizations are not considered SAEs in BMS clinical studies: 

a visit to the emergency room or other hospital department <24 hours, that does not 
result in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status (eg, 
routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry 
into the study. Appropriate documentation is required in these cases.

admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (eg, lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason)

admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
Results in persistent or significant disability or permanent damage
Is a congenital anomaly/birth defect
Is an important medical event (defined as a medical event[s] that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above). Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization. Potential drug-induced liver injury (DILI) is also considered an important 
medical event (see Section 8.2.8 for the definition of potential DILI). 
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Pregnancy and potential DILI must follow the same transmission timing and processes to BMS as 
used for SAEs (see Section 8.2.6 for reporting pregnancies).
EVALUATING AES AND SAES
Assessment of Intensity
The intensity of AEs is determined by a physician and will use the following levels:

Mild: An event that is easily tolerated by the subject, causing minimal discomfort, and not 
interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with an SAE. Severe is a category utilized for rating the intensity of 
an event; and both AEs and SAEs can be assessed as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. A “reasonable possibility of a relationship” conveys that there 
are facts, evidences, and/or arguments to suggest a causal relationship rather than a 
relationship cannot be ruled out.  

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that 
the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
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Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. Note: Follow-
up SAE reports must include the same investigator term(s) initially reported. 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS (or 
designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
REPORTING OF SAES TO SPONSOR OR DESIGNEE
SAEs, whether related or not related to study drug, and pregnancies must be reported to PRA 
Drug Safety within 24 hours of awareness of the event.
SAEs must be recorded on the SAE Report Form. For studies capturing SAEs through electronic 
data capture, electronic submission is the required method for reporting. In the event the 
electronic system is unavailable for transmission, paper forms must be used and submitted 
immediately. When paper forms are used, the original paper forms are to remain on site.
Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via email 
or confirmed facsimile (fax) transmission to:
SAE Email Address: BMSSafety@prahs.com
SAE Fax Number: 
Americas: 1-888-772-6919 (or 1-434- 951-3482)
Europe/East Asia-Pacific: +44-1792-525-720 
SAE Telephone Contact - For questions on SAE/pregnancy reporting, please call:
Americas: 1-800 772 2215 (or 1-434-951-3489)
Europe/East Asia-Pacific: +49-621-878-2154.
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP:

Premenarchal

Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the subject’s medical records, 
medical examination, or medical history interview.

Postmenopausal female

A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle-stimulating hormone (FSH) level 
>40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout periods below are suggested guidelines and the investigators should use their 
judgment in checking serum FSH levels. 

1-week minimum for vaginal hormonal products (rings, creams, gels)

4-week minimum for transdermal products

8-week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is >40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
CONTRACEPTION GUIDANCE FOR FEMALE SUBJECTS OF CHILD BEARING 
POTENTIAL
One of the highly effective or less than highly effective methods of contraception listed below is 
required during study duration and until the end of relevant systemic exposure, defined as 3 days 
after the end of study treatment, plus 30 days.
Local laws and regulations may require use of alternative and/or additional contraception methods
(eg, one highly effective method plus another method).
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Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of <1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation

oral 

intravaginal 

transdermal 

Combined (estrogen- and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of therapy

Progestogen-only hormonal contraception associated with inhibition of ovulation

oral 

injectable 

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy
Highly Effective Methods That Are User Independent

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation

Intrauterine device (IUD)b

Intrauterine hormone-releasing system (IUS)b

Bilateral tubal occlusion

Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. 

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 treatment. 
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 subject.

It is not necessary to use any other method of contraception when complete abstinence is 
elected. 

WOCBP subjects who choose complete abstinence must continue to have pregnancy tests, 
as specified in Section 1.3. 

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP subjects chooses to forego complete abstinence 
NOTES: 
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 subjects participating in clinical studies.
b  Intrauterine devices and intrauterine hormone-releasing systems are acceptable methods of contraception in the 
absence of definitive drug interaction studies when hormone exposures from intrauterine devices do not alter 
contraception effectiveness.
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Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of >1% per year when used consistently and correctly.

Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal Sponge with spermicide

Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action
Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus interruptus).

Spermicide only

Lactation amenorrhea method (LAM)
CONTRACEPTION GUIDANCE FOR MALE SUBJECTS WITH PARTNER(S) OF 
CHILD BEARING POTENTIAL.
Male subjects with female partners of childbearing potential are eligible to participate if they agree 
to the following during the treatment and until the end of relevant systemic exposure.

Inform any and all partner(s) of their participation in a clinical drug study and the need to 
comply with contraception instructions as directed by the investigator.

Female partners of males participating in the study to consider use of effective methods of 
contraception until the end of relevant systemic exposure, defined as the duration of study 
treatment.

Condom use is not required.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 8.2.6 and APPENDIX 3.
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APPENDIX 5
BRITISH ISLES LUPUS ASSESSMENT GROUP (BILAG)-2004
(For Reference Use Only)
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APPENDIX 6
SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY 
INDEX 2000
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APPENDIX 7
CUTANEOUS LUPUS ERYTHEMATOSUS DISEASE AREA AND 
SEVERITY INDEX (CLASI)
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APPENDIX 8
VISUAL ANALOG SCALE FOR PHYSICIAN’S GLOBAL 
ASSESSMENT OF DISEASE ACTIVITY
(For Reference Use Only)
The physician’s global assessment of disease activity will be measured with a 4-point visual 
analog scale evaluating average SLE disease severity over the last 4 weeks.
How do you assess your patient’s (the subject’s) current disease activity as compared to the 
last visit? Please mark the line below.
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APPENDIX 9
SYSTEMIC LUPUS INTERNATIONAL COLLABORATING 
CLINICS/ AMERICAN COLLEGE OF RHEUMATOLOGY 
DAMAGE INDEX
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APPENDIX 10
PATIENT-REPORTED OUTCOMES MEASUREMENT 
INFORMATION SYSTEM (PROMIS) FATIGUE
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APPENDIX 11
TUBERCULOSIS RISK ASSESSMENT TOOL
A subject with any of the 3 following high-risk factors will have an interferon gamma release assay
(IGRA):
Yes
No
1. Recent close or prolonged contact with someone with infectious TB disease
2. High-risk profession or situations, like being patient-facing, eg, healthcare
providers
3. Recent travel to or from a high burden country for TB (please see country list 
from UN partner website [Stop TB]):  
http://www.stoptb.org/countries/tbdata.asp
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