Clinical trial NCT03252587
Conditions: Systemic Lupus Erythematosus
Sponsor: Bristol-Myers Squibb
Start date: 2017-09-21; Completion date: 2021-10-28
Enrollment: 363 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will investigate BMS-986165 to assess its effects in participants with systemic lupus erythematosus (SLE).

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None arm 4: None
Interventions: intervention 1: BMS-986165 intervention 2: Placebo
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days

Protocol documents:
Prot_000.pdf: 
Official Title of Study: 
 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and 
Safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus 
 
NCT Number: NCT03252587 
 
Document Date (Date in which document was last revised): April 15, 2020 


Protocol Number:
IM011021
IND Number:
134253
EX-US
Non-IND
EUDRACT Number:
2017-001203-79
Date; Version:
15-Apr-2020; IM011021–Revised Protocol 04 Final Approved
Clinical Protocol IM011021
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and 
Safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus
24-hr Emergency Telephone Number
North America: 
Asia-Pacific: 
Bristol-Myers Squibb Research and Development
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
6-5-1 Nishi-Shinjuku, Shinjuku-ku,
Tokyo, 163-1328, Japan
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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Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
2
DOCUMENT HISTORY
Document
Date of Issue
Approver(s)
Summary of Change
Original Protocol
23-May-2017
Not applicable
Japan Protocol 
Amendment 01
23-Aug-2017
Japan specific
Global
Revision 01 
(Version 2.0)
24-Jan-2018
Updated the Sponsor’s protocol 
template, style, and made typographic 
corrections throughout the protocol; 
revised study design including sample 
size reduction to 360, decreased 
frequency of 12 mg arm to QD, and 
changed primary objective to SRI(4) 
response; clarified and updated certain 
procedures; revised certain 
inclusion/exclusion for clarity; revised 
certain appendices based on updates 
throughout Innovative Medicines 
Development
Japan Protocol 
Amendment 02
28-Mar-2018
Japan specific
Japan Protocol 
Amendment 03
26-Jun-2018
Japan specific
Global
Revision 02
(Version 3.0)
28-Jan-2019
Updated the Sponsor’s contact 
information; made typographic 
corrections to the protocol; clarified 
certain procedures; changed LLDAS 
 to a secondary 
endpoint; redefined partial and major 
clinical response; revised certain 
inclusion/exclusion criteria for clarity; 
updated wording in Appendix 3 and 
Appendix 4 to be consistent across 
studies of BMS-986165
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BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
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Document
Date of Issue
Approver(s)
Summary of Change
Global
Revision 03
(Version 4.0)
11-Jun-2019
Updated the Document History to 
include several Japan-specific 
amendments
Restored the Photography assessment 
in Table 3 (Week 28/Day197 Visit), 
which was inadvertently omitted in 
v3.0 
 
 
Clarified Inclusion Criteria regarding: 
x
Loss of functional range of
movements and daily activity
(SLE Disease Characteristics in
Inclusion Criterion 2)e)ii);
Section 5.1)
x
Use of corticosteroid
monotherapy (Medications for
SLE in Inclusion Criterion 3)b);
Section 5.1)
x
Use of effective methods of
contraception (Age and
Reproductive Status in Inclusion
Criterion 4)f) and 4)g);
Section 5.1)
Removed language regarding 
prohibition of P-glycoprotein 
inhibitors (item #7, Section 6.7.1)
based on recent drug-drug interaction 
data 
Revised the definition of an overdose 
to align with a revision of appendices 
across IMD; overdose is no longer 
reported automatically as a serious 
adverse event (Section 8.4)
 
 
Clarified that plasma concentration 
values (rather than just Ctrough 
values) will be summarized 
(Section 9.3.3.1)
Aligned APPENDIX 4 language 
regarding male subjects with female 
partner(s) of childbearing potential 
with current safety guidance. 
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BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
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Document
Date of Issue
Approver(s)
Summary of Change
Protocol 
Amendment 07a
30-Jul-2019
South Korea and Taiwan-specific 
amendment to modify inclusion 
criterion regarding age and to include 
hepatitis B surface antibody screening 
and hepatitis B virus DNA screening 
and monitoring.
Global
Revision 04
im011021-
revprot04b
15-Apr-2020
Updated the Study Director and 
Approver information;
 
 
 clarified PK sampling 
windows; synchronized sample size 
determination with testing hierarchy; 
updated adjustments for multiplicity.
aRevision numbering has been updated to reflect total number of revisions.
bProtocol numbering format has been updated. Legacy 
 numbering is provided for consistency.
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BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
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SUMMARY OF CHANGES
Rationale: 
The primary purpose of this global revised protocol is to modify the analysis plan and provide 
clarifications in the protocol.
Key modifications and clarifications are summarized as follows: 
x
Added clarifying detail to several items in the protocol
x
Changed secondary endpoints to be assessed at 48 weeks
x
Updated the sampling windows for the collection of pharmacokinetic samples at the Day 1
and Day 85 visits
x
Revised certain sub-sections within Statistical Considerations
Substantive changes made to previous versions of the protocol and the rationale for these changes 
are noted below in the summary of key changes table. All changes applied to the protocol body 
were applied to the synopsis, as necessary; synopsis changes are not included in the summary of 
key changes table. Only major additions and deletions are provided in this summary table; all 
minor grammatical, formatting, stylistic changes, or clarifications as well as organizational 
changes are not included.
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL
Section Number 
& Title
Description of Change
Brief Rationale
Title Page
Updated sponsor Study Director
Updated with current 
contact
Document History
Updated sponsor Study Approver
Updated with current 
contact
Synopsis
Updated all corresponding sections to the main report sections 
(listed below)
Rationale for changes 
included below
3 Objectives and 
Endpoints; Table
7
Revised description of pharmacokinetics objective and endpoint
Clarified that the 
active metabolite of 
BMS-986165 is 
included in the 
analysis
3 Objectives and 
Endpoints,
9.3.1.1 Endpoints
Moved Week 48 endpoints (SRI(4), BICLA, LLDAS, CLASI50,
and 40-Joint count) to multiplicity-controlled Secondary 
Endpoints (and corresponding Secondary Objectives)
 
Week 48 endpoints 
moved into the 
multiplicity-controlled 
hierarchy for better 
alignment with 
regulatory guidance 
documents
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TYK2 Inhibitor
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SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL
Section Number 
& Title
Description of Change
Brief Rationale
4.1 Overall 
Design
Removed the following sentence:
The end of the study for sample analysis is defined as 2 years after 
final clinical study report
To remove 
inconsistency as future 
sample analysis may 
be up to 15 years after 
the final clinical study 
report or as per local 
regulations
5.1 Inclusion 
Criteria
Removed criterion 4 i)
For consistency with 
male contraception 
requirements
5.5.1 Retesting 
During Screening 
Period; 
Rescreening
Updated text for rescreening subjects
Additional rescreening 
is allowed for subjects 
who may be otherwise 
eligible but experience 
an exceptional 
circumstance beyond 
site or subject control.
8.6.2 Sampling 
Windows
Updated to:
•The following windows apply to other samples:
- ±0.25 hour for the 0.5-hour sample
- ±0.5 hour for the 2-hour sample
- ±1 hour for the 4- and 6-hour samples
Added a 
pharmacokinetic 
sampling window for 
the 0.5-hour collection 
(Day 1 and Day 85) 
and modified the 2-
hour collection 
window (Day 1 and 
Day 85)
8.6.2 Sampling 
Windows
Updated to:
If samples cannot be taken within the specified time window, 
every effort should be made to take a sample as soon as
possible. Deviations from the sampling windows must be noted 
in the source documents.
To instruct sites to 
collect samples even if 
they are collected 
outside of the provided 
sample windows and 
document these 
occurrences.
9.1 Sample Size 
Determination
Updated text to include description of the BID and QD branches
The power for the 
initial statistical tests 
within each branch 
(BID, alpha=0.04 and 
QD, alpha=0.01) were 
added.
9.2 Populations 
for Analyses
The word “important” changed to “relevant” in per protocol set 
definition
Updated terminology.
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SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL
Section Number 
& Title
Description of Change
Brief Rationale
9.3.1.2
Nonresponders
Nonresponder imputation (NRI) section updated
Updated to clarify that 
this NRI is applicable 
to the primary and 
secondary endpoints at 
Week 32 and Week 
48. Further guidance
for other endpoints
/timepoints will be
provided in the SAP.
9.3.1.3 Analysis 
Methodology
Single randomization stratum combining Region (US, Latin 
America, Rest of World, Japan [other stratification factors will not 
be applied in Japan]), CS dose at baseline (≥10 mg/day or < 10 
mg/day) and SLEDAI-2K at baseline (≥ 10 or < 10) added for 
logistic regression, Cochran-Mantel-Haenszel and repeated 
measures analysis 
Clarification of how to 
handle the lack of CS 
and SLEDAI-2K 
stratification within 
Japanese subjects
9.3.5 Analysis and 
Reporting
The planned 32-week database lock has been removed.
Since the key 
secondary endpoints 
will now be assessed at 
Week 48 no database 
lock will occur until all 
randomized subjects 
have completed 48 
weeks of double-blind 
treatment (or have 
discontinued).
APPENDIX 4
Women of
Childbearing 
Potential 
Definitions and
Methods of
Contraception
Updated text to specify hormonal contraception must begin at 
least 30 days prior to initiation of study therapy
To align with informed 
consent language 
across all 
BMS-986165 studies
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TYK2 Inhibitor
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STUDY ACKNOWLEDGMENT/DISCLOSURE
I understand that this protocol contains information that is confidential and proprietary to Bristol-Myers 
Squibb Company (BMS). Any supplemental information 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 protocol.
I have read the original protocol/revised protocol and agree that it contains all necessary details for carrying 
out the study as described. I will conduct this protocol as outlined therein and will make a reasonable effort 
to complete the study within the time designated.
I will provide copies of the protocol and access to all information furnished by BMS to study personnel 
under my supervision. I will discuss this material with them to ensure that they are fully informed about the 
investigational product and the study. 
I will provide protocol information to my Institutional Review Board(s) [IRB(s)] or Independent Ethics 
Committee(s) [IEC(s]. I understand that original protocol/revised protocols must be reviewed by the 
Institutional Review Board or Independent Ethics Committee overseeing the conduct of the study and 
approved or given favorable opinion by all necessary Health Authorities before implementation unless to 
eliminate an immediate hazard to subjects.
I agree that the contents of the protocol may not be disclosed to any other person or entity or used for any 
other purpose without the prior written consent of BMS. The foregoing shall not apply to disclosure required 
by governmental regulations or laws; however, I will give prompt notice to BMS of any such disclosure.
I agree that the study data derived from this protocol may only be used and disclosed in furtherance of the 
protocol, for the medical treatment of a study subject or for publication of study results in accordance with 
the terms of the clinical trial agreement or as otherwise permitted by the terms of the clinical trial agreement.
I agree not to collect or use samples (e.g., tissue, blood, serum, urine) or collect data (other than for 
diagnostic or treatment purposes) from the study subjects while enrolled in the study, except as expressly 
permitted by the protocol or the terms of the clinical trial agreement.
I understand that I may terminate or suspend enrollment of the study at any time if it becomes necessary to 
protect the best interests of the study subjects. Unless otherwise provided in the clinical trial agreement, the 
study may be terminated at any time by BMS, with or without cause.
Original Protocol:
Revised Protocol:
Protocol Number: IM011021
Site Number: 
Date of Protocol or Revised Protocol: 15-Apr-2020
IND Number: 134253
EUDRACT Number: 2017-001203-79
Investigator: 
Date: 
(signature)
(printed name)
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TYK2 Inhibitor
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TABLE OF CONTENTS
TITLE PAGE...................................................................................................................................1
DOCUMENT HISTORY.................................................................................................................2 
SUMMARY OF CHANGES...........................................................................................................5 
TABLE OF CONTENTS.................................................................................................................9 
LIST OF TABLES.........................................................................................................................13 
LIST OF FIGURES .......................................................................................................................13 
1 
PROTOCOL SUMMARY..........................................................................................14 
1.1 
Synopsis......................................................................................................................14 
1.2 
Schema........................................................................................................................17 
1.3 
Schedules of Activities ...............................................................................................17 
2 
INTRODUCTION ......................................................................................................29 
2.1 
Study Rationale...........................................................................................................29 
2.2 
Background.................................................................................................................30 
2.2.2 
Early Clinical Experience...........................................................................................32 
2.3 
Benefit/Risk Assessment ............................................................................................34 
3 
OBJECTIVES AND ENDPOINTS............................................................................35 
4 
STUDY DESIGN .......................................................................................................38 
4.1 
Overall Design............................................................................................................38 
4.1.1 
Data Monitoring Committee and Other External Committees...................................40 
4.2 
Number of Subjects ....................................................................................................40 
4.3 
End of Study Definition..............................................................................................40 
4.4 
Scientific Rationale for Study Design ........................................................................40 
5 
STUDY POPULATION.............................................................................................42 
5.1 
Inclusion Criteria ........................................................................................................43 
5.2 
Exclusion Criteria.......................................................................................................46 
5.3 
Randomization............................................................................................................50 
5.4 
Lifestyle Restrictions..................................................................................................50 
5.5 
Screen Failures............................................................................................................50 
5.5.1 
Retesting During Screening Period; Rescreening......................................................50 
6 
TREATMENT ............................................................................................................51 
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6.1 
Treatments Administered............................................................................................53 
6.2 
Method of Treatment Assignment..............................................................................53 
6.3 
Blinding ......................................................................................................................53 
6.3.1 
Maintaining the Blind.................................................................................................53 
6.4 
Dosage Modification ..................................................................................................54 
6.5 
Preparation/Handling/Storage/Accountability............................................................55 
6.5.1 
Retained Samples for Bioavailability/Bioequivalence................................................55 
6.6 
Treatment Compliance................................................................................................55 
6.7 
Concomitant Therapy .................................................................................................55 
6.7.1 
Prohibited and/or Restricted Treatments ...................................................................55 
6.7.2 
Existing Therapies for Systemic Lupus Erythematosus..............................................56 
6.7.3 
Corticosteroid Tapering .............................................................................................57 
6.8 
Treatment After the End of the Study.........................................................................58 
7 
DISCONTINUATION CRITERIA............................................................................58 
7.1 
Discontinuation from Study Treatment ......................................................................58 
7.2 
Discontinuation from the Study..................................................................................59 
7.3 
Post Study Treatment Follow-Up...............................................................................59 
7.4 
Lost to Follow-Up.......................................................................................................60 
7.5 
Replacement of Subjects.............................................................................................60 
8 
STUDY ASSESSMENTS AND PROCEDURES......................................................60 
8.1 
Efficacy Assessments .................................................................................................60 
8.2 
Laboratory Assessments Related to SLE Disease Activity ........................................63 
8.3 
Adverse Events ...........................................................................................................63 
8.3.1 
Adverse Events of Interest ..........................................................................................63 
8.3.2 
Time Period and Frequency for Collecting AE and SAE Information .......................63 
8.3.3 
Method of Detecting AEs and SAEs............................................................................64 
8.3.4 
Follow-up of AEs and SAEs........................................................................................64 
8.3.5 
Regulatory Reporting Requirements for SAEs ...........................................................65 
8.3.6 
Pregnancy...................................................................................................................65 
8.3.7 
Laboratory Test Result Abnormalities........................................................................66 
8.3.8 
Potential Drug-Induced Liver Injury..........................................................................66 
8.3.9 
Other Safety Considerations.......................................................................................66 
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8.4 
Overdose.....................................................................................................................66 
8.5 
Safety ..........................................................................................................................67 
8.5.1 
Physical Examinations................................................................................................67 
8.5.2 
Tuberculosis Screening and Chest X-ray ...................................................................67 
8.5.3 
Clinical Safety Laboratory Assessments.....................................................................67 
8.5.4 
Imaging Safety Assessment.........................................................................................68 
8.6 
Pharmacokinetics........................................................................................................68 
8.6.1 
Sampling Schedule......................................................................................................69 
8.6.2 
Sampling Windows......................................................................................................69 
8.7 
Supplemental Assessments: Photography ..................................................................70 
8.8 
Pharmacogenomics.....................................................................................................70 
8.9 
Biomarkers..................................................................................................................70 
8.9.1 
Predictors of Response ...............................................................................................71 
8.9.2 
Pharmacodynamics and Mechanism of Action...........................................................71 
9 
STATISTICAL CONSIDERATIONS .......................................................................72 
9.1 
Sample Size Determination ........................................................................................72 
9.2 
Populations for Analyses ............................................................................................73 
9.3 
Statistical Analyses.....................................................................................................73 
9.3.1 
Efficacy Analysis.........................................................................................................74 
9.3.1.1 
Endpoints....................................................................................................................74 
9.3.1.2 
Nonresponders............................................................................................................75 
9.3.1.3 
Analysis Methodology.................................................................................................75 
9.3.2 
Safety Analyses ...........................................................................................................79 
9.3.3 
Other Analyses............................................................................................................79 
9.3.3.1 
Pharmacokinetics .......................................................................................................79 
9.3.3.2 
Pharmacodynamics.....................................................................................................79 
9.3.4 
Interim Analyses .........................................................................................................79 
9.3.5 
Analysis and Reporting...............................................................................................79 
10 
REFERENCES ...........................................................................................................80 
11 
APPENDICES ............................................................................................................83 
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APPENDIX 1 
STUDY GOVERNANCE CONSIDERATIONS......................................84 
APPENDIX 2 
ABBREVIATIONS AND TRADEMARKS .............................................91 
APPENDIX 3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING ..............................95 
APPENDIX 4 
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS 
AND METHODS OF CONTRACEPTION..............................................99 
APPENDIX 5 
SYSTEMIC LUPUS INTERNATIONAL COLLABORATING
CLINICS CLASSIFICATION CRITERIA FOR SYSTEMIC 
LUPUS ERYTHEMATOSUS.................................................................102 
APPENDIX 6 
COMMONLY USED CORTICOSTEROID EQUIVALENTS ..............104 
APPENDIX 7 
REQUIRED RECOVERY (WASHOUT) TIMES FOR SPECIFIC 
MEDICATIONS PRIOR TO SCREENING ...........................................105 
APPENDIX 8 
DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL 
DISORDERS IV ......................................................................................107 
APPENDIX 9 
INTERPRETATION OF HEPATITIS B SEROLOGIC TEST 
RESULTS ................................................................................................108 
APPENDIX 10 
BRITISH ISLES LUPUS ASSESSMENT GROUP INDEX – 2004......110 
APPENDIX 11 
SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY 
INDEX 2000 DISEASE ACTIVITY QUESTIONNAIRE......................112 
APPENDIX 12 
CUTANEOUS LUPUS ERYTHEMATOSUS DISEASE AREA 
AND SEVERITY INDEX (CLASI)........................................................114 
APPENDIX 17 
OTHER ASSESSMENTS .......................................................................128 
APPENDIX 18 
MORPHINE MILLIGRAM EQUIVALENTS FOR OPIOIDS ..............129 
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LIST OF TABLES
Table 1: Screening Procedural Outline (Protocol IM011021).......................................................18 
Table 2: Treatment Period Procedural Outline Up to Week 24 (Protocol IM011021)..................20 
Table 3: Treatment Period Procedural Outline After Week 24 (Protocol IM011021) ..................25 
Table 4: Objectives and Endpoints ................................................................................................35 
Table 5: Study Treatments for IM011021 .....................................................................................52 
Table 6: Selection and Timing of Dose .........................................................................................53 
Table 7: PK and PD Sampling Schedule for BMS-986165 and BMT-153261.............................69 
LIST OF FIGURES
Figure 1 
Study Design Schematic ............................................................................39 
Figure 2 
Testing Strategy for SRI(4) Response Rate, BID Branch..........................78 
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate 
Efficacy and Safety 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 immune-mediated diseases. Tyrosine kinase 2 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 
(IBD), 
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 systemic lupus erythematosus [SLE]) and in healthy humans.5,6
The proposed Phase 2 study in subjects with SLE will provide evidence of dose-ranging efficacy 
of BMS-986165 in this disease. Systemic lupus erythematosus is an ideal condition to evaluate the 
efficacy of the selective TYK2 inhibitor BMS-986165 for multiple reasons, as follows: 1) the 
major pathways in the TYK2 signaling cascade (Type I IFN and IL-12/23 and the downstream 
mediators IFNγ and IL-17) have been implicated in SLE disease pathogenesis;7 2) biologic agents 
targeting the IL-12/23 pathway, or the IFNα (or the Type I IFN) receptor have been shown to be 
efficacious in Phase 2 studies of SLE8; and 3) the ability to measure circulating target-specific 
(such as suppression of IFN-stimulated gene expression) and disease-specific pharmacodynamic 
(PD) measures in SLE both before and after treatment allows for establishing exposure-response 
relationships for PD endpoints in this condition.
The present study is the first study of this TYK2 inhibitor conducted in subjects with SLE and is 
intended to determine whether the pharmacological effects of TYK2 inhibition are associated with 
objective clinical improvement in SLE disease activity and related biomarkers. The study is also 
designed to assess the safety and tolerability of short- and long-term BMS-986165 treatment in 
subjects with SLE and to determine the dose level that provides the optimal balance of efficacy 
and safety.
Study Population:
The study will enroll male and female subjects, 18 to 75 years old (inclusive), with SLE defined 
as follows:
x
Meeting the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria 
for SLE9
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x
Being positive for one of the following: antinuclear antibody (ANA) ≥1:80 or positive anti-
double-stranded deoxyribonucleic acid (dsDNA; indeterminate values are considered positive)
or positive anti-Smith (Sm) as determined by the central laboratory
x
Having Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score
≥6 points and clinical SLEDAI-2K score ≥4 (points from organic brain syndrome, headache,
alopecia, and mucosal ulcers do not count towards the SLEDAI-2K score for the purposes of
inclusion)
Those with drug-induced SLE, certain other immune-mediated diseases, and active, severe lupus 
nephritis or central nervous system lupus will be excluded. To be randomized on Day 1 and to 
receive study treatment or placebo, subjects must meet criteria related to active musculoskeletal 
and/or mucocutaneous disease, with a clinical SLEDAI ≥4.
Objectives and Endpoints:
Objective
Endpoint
Primary Efficacy
x
To assess the effect of BMS-986165 on
SLE Responder Index (SRI)(4) response at
Week 32 in subjects with SLE
x
Proportion of subjects who meet response
criteria for SRI(4) at Week 32 (Section 8.1)
Secondary Efficacy
x
To assess the effect of BMS-986165 on
measures of global and organ-specific
clinical responses
x
Proportion of subjects who meet response
criteria for SRI(4) at Week 48
x
Proportion of subjects who achieve a
British Isles Lupus Assessment Group
(BILAG)-based 
Composite 
Lupus
Assessment (BICLA) response at Week 48
x
Proportion of subjects who achieve Lupus
Low Disease Activity State (LLDAS) at
Week 48
x
Proportion of subjects with a Cutaneous
Lupus Erythematosus Disease Area and
Severity Index (CLASI) activity score ≥ 10
at baseline who achieve a CLASI response,
defined as a decrease of ≥ 50% from
baseline CLASI activity score at Week 48
x
Change from baseline in the 40-joint count
for tender, swollen, and tender + swollen
joints at Week 48
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
16
Objective
Endpoint
Safety
x
To assess the safety and tolerability of 
BMS-986165
x
Number and proportion of subjects 
experiencing 
serious 
adverse 
events 
(SAEs); adverse events (AEs); and 
abnormalities in laboratory testing, vital 
signs, and electrocardiograms (ECGs)
Overall Design:
This is a randomized, placebo-controlled, double-blind, multicenter study to evaluate the efficacy 
and safety of BMS-986165 in subjects with SLE. The study includes a screening period (SP) of 
up to 4 weeks (28 days); a 48-week (336-day) blinded treatment period (TP); and a 28-day 
follow-up period (FP), for subjects who do not continue into the long-term extension (LTE) study 
(IM011074). The total duration will be approximately 56 weeks (392 days). Other details of 
study design are as follows:
x
Randomization will be performed after completion of the SP, on Day 1 of the TP.
x
Randomization in a 1:1:1:1 ratio will be performed using interactive response technology 
(IRT) and will be stratified by screening corticosteroid (CS) dose (≥10 mg/day or 
< 10 mg/day), screening SLEDAI-2K score (≥10 or < 10), and geographic region.
x
The blind will be maintained during the TP by the use of matched capsules (placebo and 3 mg
BMS-986165) provided in blister cards that are identical in appearance while providing the 
appropriate randomized dose.
x
Clinical, laboratory, and photographic evidence of disease activity will be reviewed by blinded 
external reviewers. 
x
Safety data will be reviewed by the Data Monitoring Committee.
x
The primary analysis of Week 32 efficacy assessments will be performed after all subjects 
have completed 48 weeks of double-blind treatment (or discontinued from the study).
Number of Subjects: 
Approximately 360 subjects will be randomized to receive oral treatment with BMS-986165
12 mg once daily (QD), 6 mg twice daily (BID), 3 mg BID, or placebo BID.
Treatment Arms and Duration:
Study treatment: Subjects in all treatment groups will take oral doses of the investigational
product (IP) for 48 weeks during the TP as follows: BMS-986165 12 mg QD, 6 mg BID, 3 mg
BID, or placebo BID.
Approved
1.0
v
Approved
1.0
v


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Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
18
Table 1: Screening Procedural Outline (Protocol IM011021)
Procedure
Screening Visit 
From Day -28
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed consent is signed.
Enroll subject
X
Obtain number from IRT; contact IRT to screen fail those not eligible.
Inclusion/exclusion criteria
X
Section 5
Medical history
X
Include any toxicities or allergy related to previous treatments.
SLICC criteria for SLE
X
APPENDIX 5
BILAG-2004 Index
X
APPENDIX 10
SLEDAI-2K
X
APPENDIX 11
Physician’s Global 
Assessment
X
Assessment of disease activity using a 3-point scale
40-joint count
X
Counts for tender, swollen, and tender + swollen joints (Section 8.1)
CLASI
X
APPENDIX 12; photography as needed.
Review concomitant 
medications
X
Restricted medications are detailed in APPENDIX 7. Medication restrictions at screening are in Section 6.
Safety Assessments
Physical examination
X
General, head, eyes, ears, nose, throat, neck, cardiovascular, lungs, abdominal, extremities, neurologic, 
psychiatric, skin, musculoskeletal
Physical measurements
X
Height and weight
Vital signs
X
Body temperature, respiratory rate, and blood pressure and heart rate; blood pressure and heart rate should be 
measured seated after at least 5 minutes of rest.
Electrocardiogram
X
Single 12-lead reading, recorded after the subject has been supine for at least 5 minutes
Chest X-ray
X
Can be performed within 6 months of the screening visit with documentation on file
Monitor for SAEs
X
From the signing of informed consent
Breast and cervical cancer 
screening
X
Investigators are encouraged to ensure screening is up to date according to local guidelines (women only). 
Because most patients with SLE are young women, screening for cervical and breast cancer prior to 
randomization is encouraged as per local guidelines due to the small inherent risk of increased malignancy 
with immunosuppressant agents, but this screening is at the investigator’s discretion.
Laboratory Tests
Hematology, chemistry, 
urinalysis, and coagulation
X 
Includes blood and urine samples; collect after at least 10 hours of fasting.
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
19
Table 1: Screening Procedural Outline (Protocol IM011021)
Procedure
Screening Visit 
From Day -28
Notes
Serology
X
Includes hepatitis C antibody, hepatitis B surface antigen, hepatitis B core antibody, HIV 1 and 2, 
(Section 5.2)
Tuberculosis screening
X
In accordance with standard testing (details are provided in Section 8.5.2)
Pregnancy test (urine)
X
Women of childbearing potential only
Follicle-stimulating hormone
X
Postmenopausal women only, to confirm status (APPENDIX 4)
Thyroid stimulating hormone
X
Free thyroxine will be assessed only if thyroid-stimulating hormone is abnormal.
Spot urine for 
protein:creatinine ratio
X
Serum complement (C3, C4)
X
Autoantibodies
X
ANA, anti-Ro (SSA), anti-La (SSB), anti-RNP, anti-dsDNA, anti-Sm, antiphospholipid antibodies: 
anti-cardiolipin, lupus anticoagulant, beta-2 glycoprotein 1
Coomb’s test (direct)
X
Blood sample for gene 
expression analysis
X
Required for study entry but not used for prospective subject stratification
Blood for inflammation 
markers
X
Serum and plasma
Photography
X
Subjects who consented to photography will be photographed at randomization for baseline photographs, 
including all views per the Photography Manual. Subjects with rash and/or alopecia at screening who 
consented to photography will be photographed beginning at screening. See Photography Manual for details.
ANA = antinuclear antibodies; anti-Sm = anti-Smith; BILAG = British Isles Lupus Assessment Group; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity 
Index; dsDNA = double-stranded deoxyribonucleic acid; HIV = human immunodeficiency virus; IRT = interactive response technology; RNP = ribonucleoprotein; SAE = serious 
adverse event; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC = Systemic Lupus International 
Collaborating Clinics
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
20
Table 2: Treatment Period Procedural Outline Up to Week 24 (Protocol IM011021)
Procedure
Week 0
D1
Week 2
D15
(±3 d)
Week 4
D29
(±3 d)
Week 8
D57
(±3 d)
Week 12
D85
(±3 d)
Week 16
D113
(±3 d)
Week 20
D141
(±3 d)
Week 24
D169
(±3 d)
Notes
Eligibility/randomization 
criteria
X
Confirm eligibility criteria and assess 
randomization criteria (Section 5.3). All 
procedures to be completed before 
dosing unless otherwise specified
Safety Assessments
Complete PE
X
General, head, eyes, ears, nose, throat, 
neck, cardiovascular, lungs, abdominal, 
extremities, neurologic, psychiatric, 
skin, musculoskeletal
Targeted PE
X
X
X
X
X
X
X
General, eyes, throat, cardiovascular, 
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
X
See note in Table 1
Electrocardiogram
X
X
X
X
See note in Table 1
Concomitant medication use
X
X
X
X
X
X
X
X
Monitor for AEs and SAEs
X
X
SAEs from the signing of informed 
consent; AEs from time of first dose of 
the IP
Laboratory Tests
Predose (note in Table 1; Section 8.5.3)
Hematology, chemistry, 
urinalysis, coagulation
X
X
X
X
X
X
X
X
Fasting lipid panel
X
X
Predose, after at least a 10-hour fast
Fasting plasma glucose
X
X
After at least a 10-hour fast
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
21
Table 2: Treatment Period Procedural Outline Up to Week 24 (Protocol IM011021)
Procedure
Week 0
D1
Week 2
D15
(±3 d)
Week 4
D29
(±3 d)
Week 8
D57
(±3 d)
Week 12
D85
(±3 d)
Week 16
D113
(±3 d)
Week 20
D141
(±3 d)
Week 24
D169
(±3 d)
Notes
Pregnancy test (WOCBP only)
X
X
X
X
X
X
X
X
APPENDIX 4
Spot urine for protein creatinine 
ratio
X
X
X
X
X
X
X
Coomb’s Test (direct)
X
X
X
X
X
X
X
hsCRP
X
X
X
TBNK
X
X
X
Serum Ig
X
X
X
X
IgM, IgA, IgG, IgE
PK Assessments
X
X
X
X
X
X
Note: Fasting is required for Day 1 and 
Day 85. See Section 8.6
Biomarker Assessments
Serum Complement
X
X
X
X
X
X
X
X
C3, C4
Anti-dsDNA autoantibodies
X
X
X
X
X
X
X
Blood RNA for IRG and 
steroid signature, and genome-
wide expression
X
X
X
X
Xa
X
X
X
PD assessment of IRG, steroid 
signature, and genome-wide expression 
analysis; predose; (Section 8.9). 
 
ollection is to be anytime within 
the window, regardless of dosing time 
on the day of collection.
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
22
Table 2: Treatment Period Procedural Outline Up to Week 24 (Protocol IM011021)
Procedure
Week 0
D1
Week 2
D15
(±3 d)
Week 4
D29
(±3 d)
Week 8
D57
(±3 d)
Week 12
D85
(±3 d)
Week 16
D113
(±3 d)
Week 20
D141
(±3 d)
Week 24
D169
(±3 d)
Notes
Efficacy Assessments
NSAIDs must be withheld for 
≥12 hours before visits.
BILAG-2004 Index
X
X
X
X
X
X
X
SLEDAI-2K
X
X
X
X
X
X
X
Physician’s Global Assessment
X
X
X
X
X
X
X
Assessment of disease activity using a 
3-point scale (0 to 3)
40-joint count
X
X
X
X
X
X
X
See note in Table 1.
CLASI
X
X
X
X
X
X
X
APPENDIX 12
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
23
Table 2: Treatment Period Procedural Outline Up to Week 24 (Protocol IM011021)
Procedure
Week 0
D1
Week 2
D15
(±3 d)
Week 4
D29
(±3 d)
Week 8
D57
(±3 d)
Week 12
D85
(±3 d)
Week 16
D113
(±3 d)
Week 20
D141
(±3 d)
Week 24
D169
(±3 d)
Notes
Photography
X
X
X
X
X
X
X
Subjects who consented to photography 
will be photographed at randomization 
for baseline photographs, including all 
views per the Photography Manual. 
Subjects with rash and/or alopecia at 
screening who consented to 
photography will be photographed 
beginning at screening. See 
Photography Manual for details.
Assess suitability for CS taper
(X)
(X)
(X)
X
X
X
X
Taper is not required to start until 
Week 8. The CS dose must remain 
stable from Week 20 to 32.
Patient’s Global Assessment
X
X
X
X
X
X
X
Assessment of disease activity using a 
visual analog scale (APPENDIX 17)
Pain assessment
X
X
X
X
X
X
X
Using a numerical rating scale 
(APPENDIX 17)
Clinical Drug Supplies
Randomization
X
Using IRT
Dispense Study Treatment
X
X
Study treatment dispensed on Day 169 
for the continued TP (Table 3)
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
24
Table 2: Treatment Period Procedural Outline Up to Week 24 (Protocol IM011021)
Procedure
Week 0
D1
Week 2
D15
(±3 d)
Week 4
D29
(±3 d)
Week 8
D57
(±3 d)
Week 12
D85
(±3 d)
Week 16
D113
(±3 d)
Week 20
D141
(±3 d)
Week 24
D169
(±3 d)
Notes
Study Treatment 
Administration
X
X
Study Treatment Compliance
X
X
X
X
X
X
X
AE = adverse event; ANA = antinuclear antibodies; anti-Sm = anti-Smith; BILAG = British Isles Lupus Assessment Group; CLASI = Cutaneous Lupus Erythematosus Disease Area and 
Severity Index; CS = corticosteroid; dsDNA = double-stranded deoxyribonucleic acid; 
 hsCRP = high-sensitivity C-reactive protein; 
Ig = immunoglobulin; IP = investigational product; IRG = interferon-regulated genes; IRT=interactive response technology; 
 
NSAID = nonsteroidal anti-inflammatory drug; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
 
 RNA = ribonucleic acid; RNP = ribonucleoprotein; SAE = serious adverse event; 
 SLEDAI-2K = Systemic Lupus 
Erythematosus Disease Activity Index 2000; SLICC = Systemic Lupus International Collaborating Clinics; TBNK = T cells, B cells, and natural killer cells; TP = treatment period; 
WOCBP = women of childbearing potential
aIntensive PD sampling on Day 85 is further described in Table 7.
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
25
Table 3: Treatment Period Procedural Outline After Week 24 (Protocol IM011021)
Procedure
Week 28
D197
(±3 d)
Week 32
D225
(±3 d)
Week 36
D253
(±3 d)
Week 40
D281
(±3 d)
Week 44
D309
(±3 d)
Week 48
D337/EOT
(±3 d)
FP
(28 days 
after EOT)a
Notes
Safety Assessments
Complete PE
X
X
General, head, eyes, ears, nose, 
throat, neck, cardiovascular, 
lungs, abdominal, extremities, 
neurologic, psychiatric, skin, 
musculoskeletal
Targeted PE
X
X
X
X
X
General, eyes, throat, 
cardiovascular, 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
See note in Table 1.
Electrocardiogram
X
X
See note in Table 1.
Concomitant medication use
X
X
X
X
X
X
X
Monitor for AEs and SAEs
X
X
Laboratory Tests
See note in Table 1.
Hematology, chemistry, 
urinalysis, coagulation
X
X
X
X
X
X
X
Fasting lipid panel
X
X
Fasting plasma glucose
X
X
Pregnancy test (WOCBP only)
X
X
X
X
X
X
X
See note in Table 1.
Spot urine for protein creatinine 
ratio
X
X
X
X
X
X
X
Coomb’s Test (direct)
X
X
X
X
X
X
X
hsCRP
X
X
X
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
26
Table 3: Treatment Period Procedural Outline After Week 24 (Protocol IM011021)
Procedure
Week 28
D197
(±3 d)
Week 32
D225
(±3 d)
Week 36
D253
(±3 d)
Week 40
D281
(±3 d)
Week 44
D309
(±3 d)
Week 48
D337/EOT
(±3 d)
FP
(28 days 
after EOT)a
Notes
TBNK
X
X
Serum Ig
X
X
X
IgM, IgA, IgG, IgE
PK Assessments
X
X
See Section 8.6
Biomarker Assessments
Serum Complement
X
X
X
X
X
X
X
C3, C4
Anti-dsDNA autoantibodies
X
X
X
X
X
X
X
Blood RNA for IRG, steroid 
signature, and genome-wide 
expression
X
X
X
X
X
X
X
Assessment of IRG, steroid 
signature, and genome-wide 
expression; predose (Section 8.9)
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
27
Table 3: Treatment Period Procedural Outline After Week 24 (Protocol IM011021)
Procedure
Week 28
D197
(±3 d)
Week 32
D225
(±3 d)
Week 36
D253
(±3 d)
Week 40
D281
(±3 d)
Week 44
D309
(±3 d)
Week 48
D337/EOT
(±3 d)
FP
(28 days 
after EOT)a
Notes
Efficacy Assessments
NSAIDs must be withheld for 
≥12 hours before visits.
BILAG-2004 Index
X
X
X
X
X
X
X
SLEDAI-2K
X
X
X
X
X
X
X
Physician’s Global Assessment
X
X
X
X
X
X
X
Assessment of disease activity 
using a 3-point scale (0 to 3)
40-joint count
X
X
X
X
X
X
X
See note in Table 1.
CLASI
X
X
X
X
X
X
X
APPENDIX 12
Photography
X
X
X
X
X
X
X
Subjects who consented to 
photography will be photographed 
at randomization for baseline 
photographs, including all views 
per the Photography Manual. 
Subjects with rash and/or alopecia 
at screening who consented to 
photography will be photographed 
beginning at screening. See 
Photography Manual for details.
Assess suitability for CS taper
X
X
X
X
CS dose must remain stable 
Weeks 20–32 and 40–48.
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
28
Table 3: Treatment Period Procedural Outline After Week 24 (Protocol IM011021)
Procedure
Week 28
D197
(±3 d)
Week 32
D225
(±3 d)
Week 36
D253
(±3 d)
Week 40
D281
(±3 d)
Week 44
D309
(±3 d)
Week 48
D337/EOT
(±3 d)
FP
(28 days 
after EOT)a
Notes
Patient’s Global Assessment
X
X
X
X
X
X
X
Assessment of disease activity 
using a visual analog scale 
(APPENDIX 17)
Pain assessment
X
X
X
X
X
X
X
Using a numerical rating scale 
(APPENDIX 17)
Clinical Drug Supplies
Dispense Study Treatment
X
X
X
X
X
Study Treatment Administration
X
X
X
X
X
X
Study Treatment Compliance
X
X
X
X
X
X
ACR = American College of Rheumatology; AE = adverse event; ANA = antinuclear antibodies; anti-Sm = anti-Smith; BILAG = British Isles Lupus Assessment Group; 
CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; CS = corticosteroid; dsDNA = double-stranded deoxyribonucleic acid; EOT = End of Treatment; 
FP = follow-up period; hsCRP = high-sensitivity C-reactive protein; Ig = immunoglobulin; IRG = interferon-regulated gene; 
 
NSAID = nonsteroidal anti-inflammatory drug; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
 
 RNA = ribonucleic acid; RNP = ribonucleoprotein; SAE = serious adverse event; 
 
SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC = Systemic Lupus International Collaborating Clinics; TBNK = T cells, B cells, and natural 
killer cells; WOCBP = women of childbearing potential
a Only for subjects not continuing in the long-term extension study IM011074
Approved
1.0
v
Approved
1.0
v


Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
29
2
INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic progressive immune-mediated disease 
characterized by pleiotropic organ/tissue involvement and clinical manifestations that 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. SLE prevalence in the United States is 
estimated at 20 to 150 cases per 100,000, and incidence is estimated at 1 to 25 per 100,000. Women 
are more frequently affected than men (9:1), as are people of African American and African 
Caribbean descent, and peak incidence occurs around the third or fourth decade of life. 
Autoantibodies that define the autoimmune nature of SLE have been identified. However, these 
autoantibodies are not specific to SLE. This and the variable clinical manifestations of SLE 
contribute to the complexity of diagnosis and treatment.
Current therapies are unsatisfactory, and include immunosuppressive drugs and corticosteroids 
(CS), 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. One goal in the management of SLE is to achieve 
disease and symptom control while minimizing CS exposure. Treatments include antimalarials, 
immunosuppressants, biologics including belimumab, and other agents (prescribed off-label). 
There remains an unmet need for novel, well-tolerated, orally administered therapies that can 
effectively modify the disease course and control symptoms.
2.1
Study Rationale
BMS-986165 is a potent, highly selective small molecule inhibitor of tyrosine kinase 2 (TYK2), 
which functions as a critical mediator in signaling pathways that regulate diverse, yet specific, 
immunomodulatory cellular responses, such as immunity, inflammation, and anti-inflammatory 
responses. BMS-986165 is the first, potent, oral TYK2 inhibitor with a novel, highly selective 
mechanism of action that has the potential to safely and effectively treat a broad spectrum of 
immune-mediated diseases. Tyrosine kinase 2 activates signal transducer and activator of 
transcription (STAT)-dependent transcription and functional responses downstream of critical 
immune mediators, such as interleukin (IL)-12, IL-23, and Type I and III interferons (IFNs). 
BMS-986165 inhibits TYK2 through a novel allosteric mechanism, binding to the unique Janus 
kinase (JAK) homology 2 (JH2) domain, rather than binding directly to the active site.1, 2, 3 TYK2 
mediates immune and inflammatory signaling pathways critical in the pathophysiology of various 
immune-mediated diseases including psoriasis, lupus, spondyloarthritis, inflammatory bowel 
disease (IBD), 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 psoriasis, colitis, and lupus; and in healthy human volunteers.5,6
The proposed Phase 2 study in subjects with SLE will provide evidence of biologic activity of 
BMS-986165 in a relevant disease population and will facilitate dose ranging for future studies in 
SLE and other immune-mediated conditions. SLE is an ideal condition to evaluate the efficacy of 
the TYK2 inhibitor BMS-986165 for multiple reasons, as follows: 1) The major pathways in the 
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TYK2 signaling cascade (Type I IFN and IL-12/23 and the downstream mediators IFNγ and IL-17) 
have been implicated in SLE disease pathogenesis,7 2) Biologic agents targeting the IL-12/23
pathway, or the IFNα (or the Type I IFN) receptor are under investigation and have been shown to 
be efficacious in the treatment of SLE based on some Phase 2 data that have been released. Thus, 
it is feasible that SLE patients treated with BMS-986165 may derive therapeutic benefit, 3) It is 
also conceivable that TYK2 inhibition may show improved benefits over existing anti-IFN 
monoclonal antibody therapies because of combined blocking effects on both the IL-12/23 and 
Type I IFN pathways,8 4) The ability to measure circulating target-specific (such as suppression 
of IFN-stimulated gene expression) and disease-specific pharmacodynamic (PD) measures in SLE 
both before and after treatment allows for establishing exposure-response relationships for PD 
endpoints.
The present study is the first study of this TYK2 inhibitor conducted in subjects with SLE and is 
intended to determine whether the pharmacological effects of TYK2 inhibition are associated with 
objective clinical improvement in SLE disease activity and related biomarkers. The study is also 
designed to assess the safety and tolerability of short- and long-term BMS-986165 treatment in 
subjects with SLE, and to determine the dose level that provides the optimal balance of efficacy 
and safety.
Research statement: The proportion of subjects with SLE who meet the response criteria for the 
SLE Responder Index (SRI[4]) at Week 32 will be greater with at least 1 of the BMS-986165
regimens than with placebo.
2.2
Background
Tyrosine kinase 2 (a member of the JAK family) catalyzes the phosphorylation of STAT proteins 
downstream of the receptors for the p40-containing cytokines IL-12 and IL-23 as well as the Type I
IFN receptor, resulting in the activation of STAT-dependent transcription and functional responses 
specific for those receptors. BMS-986165 is a first-in-class orally administered small molecule 
inhibitor of TYK2 that has been shown to be superior to blockade of the Type I IFN receptor in an 
IFN-dependent mouse model of SLE.
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2.2.2
Early Clinical Experience
The clinical data available to date supporting the safety, pharmacokinetics (PK), and PD of 
BMS-986165 are from 5 Phase 1 studies of BMS-986165 in healthy volunteers (IM011002, 
IM011015, IM011016, IM011031, and IM011039) and a Phase 2 study in adult subjects with 
moderate-to-severe psoriasis (IM011011).
Study IM011002 (Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, 
PK, and PD of BMS-986165 in Healthy Subjects) used 1, 3, 10, 20, and 40 mg doses for the 
single-dose part and 2, 4, 6, or 12 mg BID or 12 mg once daily (QD) for 14 days for the multiple 
ascending dose part. All reported adverse events (AEs) were mild or moderate in severity, and 
approximately half of subjects overall had at least 1 AE that was considered potentially related to 
study treatment. The most frequently reported AEs with single dosing were headache and 
dyspepsia. The most frequently reported AEs with multiple dosing were headache, skin rash and 
acne, and upper respiratory tract infection. Dose-limiting AEs in the form of skin rashes and 
acneiform lesions were observed. These observations were largely reported for subjects in the 
24 mg/day (12 mg BID) group and were reported for most subjects dosed at this level. These events 
had not been observed earlier in the monkey studies. These AEs were mild or moderate in nature 
and resolved with topical treatments (corticosteroid applications, benzoyl peroxide cream, 
clindamycin solution, chlorhexidine ointment). All events requiring treatment responded 
appropriately and rarely resulted in discontinuation of study drug. Overall, BMS-986165 was 
found to have an acceptable safety profile, and the acneiform lesions that were seen at the highest 
doses were manageable with topical treatments, were reversible, and were not serious or severe.
Study IM011016 (Pharmacokinetics and Metabolism of [14C] BMS-986165 in Healthy Male 
Participants) used a single dose of 24 mg [14C] BMS-986165 containing approximately 100 μCi 
of total radioactivity. Five of the 6 enrolled subjects reported mild diarrhea (loose stools), and 1 of 
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the 5 also had mild palpitations and moderate emesis. No deaths or discontinuations due to AEs 
were reported. 
Study IM011015 (The Effect of BMS-986165 on the Pharmacokinetics of Rosuvastatin) used a 
12 mg QD dose administered with 10 mg rosuvastatin in 20 healthy subjects and showed that 
BMS-986165 had no impact on exposure to rosuvastatin. Fifteen of 17 subjects who completed 
the study experienced an AE of acne, and all these AEs were mild or moderate in severity. Subjects 
with no or mild acne at baseline developed either mild or moderate acne, whereas subjects with 
moderate acne at baseline generally experienced less worsening of their acne as the study 
progressed. In 2 subjects, an AE of moderate acne led to discontinuation of study medication. All 
events of acne that required treatment responded to topical treatment. 
In Study IM011039 (The Effect of BMS-986165 on the Pharmacokinetics of a Combined Oral 
Contraceptive), healthy subjects received 24 mg/day (12 mg BID). Acneiform lesions (eg, skin 
rashes or pustules) were seen in all subjects at this dose and the number of events was similar to 
that in Study IM011002. According to the investigator, subjects typically reported light itching of 
the skin within 12 hours after the first dose of BMS-986165, followed by the acneiform dermatitis 
eruptions in face/hairline-scalp, neck, and back on Day 2 or Day 3 of dosing. Less frequently, the 
breast, arms, or abdomen were involved. The AE intensity was based on the severity of the lesion 
and the extent of body surface area affected. Bacterial cultures taken from a few of these lesions 
were negative. All lesions responded well to topical treatment and did not lead to discontinuation 
of study medication. No new skin eruptions appeared after 3 days after last dose, and all events 
resolved. All reactions were again mild or moderate and were managed with topical treatments.
Study IM011011 is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel 
group study to evaluate the clinical efficacy, safety, and PD of BMS-986165 after 12 weeks of 
treatment with 4 weeks’ follow-up in 267 subjects with moderate-to-severe psoriasis. The study 
met its primary and secondary efficacy endpoints of clinically relevant improvement in Psoriasis 
Activity and Severity Index and static Physician Global Assessment scores for 4 of the 5 doses 
investigated (only the 3 mg every other day dose did not meet the primary endpoint). The most 
common AEs reported overall were nasopharyngitis, upper respiratory tract infection, diarrhea, 
and nausea. The majority of the AEs reported in the study were mild or moderate in intensity. The 
acneiform dermatitis AEs appeared to be dose related, and most were reported for subjects in the 
2 highest dose groups. Most of the lesions were completely resolved (a few were almost 
completely resolved) with topical treatments and did not result in discontinuation of the study 
treatment. Several of the verbatim reported terms for the acneiform dermatitis group were similar 
to those previously reported for healthy subjects in Studies IM011002, IM011015, IM011031, and 
IM011039: “acne on face neck and back,” “pustular eruptions in face, neck and back” (sometimes 
including arms), or “folliculitis;” the similarity of these terms and a clear dose dependency suggest 
a common etiopathogenesis. 
In summary, BMS-986165 has demonstrated promising clinical efficacy in the treatment of 
patients with moderate-to-severe psoriasis. Acneiform skin reactions have been observed across 
the early clinical trials of BMS-986165. The reactions appear to be dose related, with the highest 
incidence at the 12 mg BID dose. All of the reactions have been mild or moderate, nonserious, 
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reversible, and have rarely led to discontinuation of study treatment. There have been no signs or 
symptoms of circulatory or respiratory impairment and no suggestions of a systemic 
hypersensitivity reaction. The acneiform skin reactions requiring treatment have been well 
managed with topical treatment such as benzoyl peroxide cream, clindamycin solution, 
chlorhexidine ointment, salicylic acid ointment, or retinoid gel. The likely mechanism(s) behind 
the acneiform dermatitis is not currently known. 
In assessments of PK in Study IM011002, BMS-986165 achieved maximum plasma 
concentrations (Cmax) approximately 1 to 2 hours after dosing and had a median terminal half-life 
ranging from 8 to 15 hours across the dose range tested. With single dosing, BMS-986165
exposures appeared to increase in a greater than dose-proportional manner at doses less than 3 mg,
and in an approximately dose-dependent manner from 3 to 40 mg. After multiple-day dosing, 
BMS-986165 accumulation in the 1.4× to 1.9× range was observed at steady state. BMS-986165
is metabolized by multiple metabolic pathways, but it does not inhibit cytochrome P450 (CYP450) 
enzymes at expected plasma concentrations. When taken with a high-fat meal, BMS-986165
exhibited a lower Cmax and a delayed time to maximum plasma concentration (Tmax) relative to 
dosing in the fasted state. Although the area under the concentration-time curve extrapolated to 
infinity (AUC[0-INF]) was decreased by 15% in the fed state relative to the fasted state, this 
difference was not thought to be clinically meaningful.
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
At this early 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 and within exposure margins 
based on comparisons of systemic exposure and body surface area.
The effects of TYK2 inhibition by BMS-986165 have been documented in pharmacology studies, 
and the potential for benefit in SLE has been suggested by nonclinical studies using a mouse model 
of SLE; further support is found in mouse models of other immune-mediated diseases. Findings in 
toxicology studies were consistent with expectations based on the pharmacology of BMS-986165.
Thus, the FIH study was conducted with standard safeguards within a range of dose regimens. 
Even at the highest exposures in healthy subjects, AEs were mild to moderate, reversible, and 
consistent with expectations based on nonclinical experience.
The risk for PK drug-drug interactions (DDIs) with BMS-986165 was assessed based on regulatory 
guidelines. At the maximum concentrations expected in this study (in portal vein or systemic 
circulation, as appropriate), the potential for DDIs involving most transporters is low. 
BMS-986165 is a breast cancer resistance protein (BCRP) inhibitor with an in vitro 50% inhibitory 
concentration of 0.31 μM. The impact of BMS-986165 on the exposures of potential concomitant 
medications that are sensitive BCRP substrates, such as rosuvastatin, is expected to be low. Data 
from a clinical DDI study that assessed the effect of BMS-986165 on rosuvastatin PK showed less 
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than 10% increase in exposures of rosuvastatin. Because of potential PK interactions with the 
transporter P-glycoprotein (P-gp) as substrate, concomitant use of strong inhibitors of P-gp is 
prohibited throughout the study. Treatment with BMS-986165 is not expected to diminish the 
effectiveness of contraceptives.
Nonclinical data and clinical experience in healthy subjects in combination with the design and 
doses selected for the current Phase 2 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 ENDPOINTS
Table 4: Objectives and Endpoints
Objectives
Endpoints
Primary Efficacy
x
To assess the effect of BMS-986165 on the 
SRI(4) response at Week 32 in subjects with 
SLE
x
Proportion of subjects who meet response 
criteria for SRI(4) (Section 8.1) at Week 32
Secondary Efficacy
x
To assess the effect of BMS-986165 on 
measures of global and organ-specific SLE 
clinical response
x
Proportion of subjects who meet response 
criteria for SRI(4) at Week 48
x
Proportion of subjects who achieve a British 
Isles Lupus Assessment Group-based 
Composite Lupus Assessment (BICLA) 
response at Week 48 after treatment with 
BMS-986165 or placebo administered on 
stable background therapy (Section 9.3.1.1)
x
Proportion of subjects who achieve Lupus 
Low Disease Activity State (LLDAS) at 
Week 48 (Section 8.1)
x
Proportion of subjects with a Cutaneous 
Lupus Erythematosus Disease Area and 
Severity Index (CLASI) activity score ≥10 at 
baseline who achieve a CLASI response, 
defined as a decrease of ≥50% from baseline 
CLASI activity score at Week 48
(Section 8.1)
x
Change from baseline in the 40-joint count for 
tender, swollen, and tender + swollen joints at 
Week 48
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Table 4: Objectives and Endpoints
Objectives
Endpoints
Safety
x
To assess the safety and tolerability of 
BMS-986165
x
Number and proportion of subjects 
experiencing serious adverse events (SAEs); 
AEs; and abnormalities in laboratory testing, 
vital signs, and electrocardiograms (ECGs) 
throughout the study
Pharmacokinetics
x
To assess PK of BMS-986165 and its active 
metabolite (BMT-153261) in subjects with 
SLE (Section 8.6)
x
Plasma concentration of BMS-986165 and 
BMT-153261
Pharmacodynamics
x
To assess the effect of BMS-986165 on PD 
markers (Section 8.9.2)
x
Change in mean and median interferon-
regulated gene (IRG) expression levels 
compared to baseline over time and at 
Week 32
x
Change in mean complement (C3, C4) and 
anti-double-stranded DNA (dsDNA) levels 
compared to baseline over time and at 
Week 32
x
Assess the effect of BMS-986165 on 
measures of global SLE clinical response in 
subjects based on IRG status (ie, high versus 
low IRG signature) at Week 32
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Table 4: Objectives and Endpoints
Objectives
Endpoints
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Table 4: Objectives and Endpoints
Objectives
Endpoints
4
STUDY DESIGN
4.1
Overall Design
This is a randomized, placebo-controlled, double-blind, multicenter study to evaluate the efficacy 
and safety of BMS-986165 in subjects with SLE. The primary study endpoint is the proportion of 
subjects who meet SRI(4) response (see Section 8.1) at Week 32 after treatment with BMS-986165 
or placebo administered on stable background therapy. This endpoint will be used to evaluate the 
research statement (Section 2.1).
The duration of study participation is approximately 56 weeks (392 days), as follows:
x
Screening period (SP): up to 4 weeks (28 days)
x
Treatment period (TP): 48 weeks (336 days) of blinded treatment
x
Follow-up period (FP): 28 days
Note: The FP is only for subjects who do not continue into the long-term extension (LTE) study 
(IM011074)
The study design schematic is presented in Figure 1.
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x
An independent data monitoring committee (DMC) will assess safety and efficacy data.
x
Physical examinations, vital sign measurements, 12-lead electrocardiograms (ECGs),
and clinical laboratory evaluations will be performed at selected times throughout the 
dosing interval. Subjects will be closely monitored for AEs throughout the study. 
Blood samples will be collected for PK and PD analyses as well.
x
Samples for biomarker assessments will be collected from a subset of subjects (those 
at USA sites only) on Day 2 or 3 (24 to 72 hours after the first dose).
4.1.1
Data Monitoring Committee and Other External Committees
An external DMC will be used in this study to perform safety monitoring by treatment group.
Unblinded data summaries and listings will be provided to the DMC to facilitate their safety 
assessment at the regularly scheduled times and on an ad hoc basis if needed. The safety review 
includes all AEs and events of interest (infections and skin reactions), focusing on early signal 
detection. Further details on the frequency, content, and methods of data reports to the DMC will 
be outlined in the DMC charter along with the processes and procedures the committee will follow.
Central Review Services (CRS) will be used in this study. The scope of responsibility will include  
 review of SLE eligibility criteri
 
 
 
.
4.2
Number of Subjects
Approximately 360 subjects will be randomized 1:1:1:1 to receive BMS-986165 12 mg QD, 
6 mg BID, 3 mg BID, or placebo BID during the TP. Sample size considerations are described in 
Section 9.1.
4.3
End of Study Definition
The duration of study participation for individual subjects is expected to be approximately 
56 weeks (392 days). 
The start of the study is defined as first visit for first subject screened. The end of the study is 
defined as the last visit or scheduled procedure shown in the Schedules of Activities (Section 1.3)
for the last subject. Study completion is defined as the final date on which data for the primary 
endpoint was expected to be collected, if this is not the same. The end of the study for analysis of 
biomarker samples is mentioned in Section 8.9.
4.4
Scientific Rationale for Study Design
The primary purpose of the study is to determine the optimal dose of BMS-986165 for treatment 
of subjects with SLE. A placebo control is included to allow the effects of treatment, both desired 
and adverse, to be appropriately attributed to treatments received. All subjects will be permitted to 
continue their existing therapies for SLE, and rescue treatments are permitted as needed (with a 
few protocol-specified limitations) to allow subjects to maintain standard disease control 
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regardless of the effects of their assigned study treatment. A plan for CS tapering is included to 
allow subjects to use the lowest dose that meets their needs throughout much of the study, but 
doses are held stable for 12 weeks before the Week 32 assessments (primary efficacy) and for 
8 weeks before the Week 48 assessments to isolate effects of assigned study treatments. A DMC 
will monitor safety and efficacy findings throughout the study to allow timely management of any 
concerns that arise. Study visits allow for close monitoring of subjects. The eligibility and 
randomization criteria are designed to ensure that subjects have the expected level of SLE disease 
activity and to minimize the risk for serious infections that may be associated with 
immunosuppressive therapies. Randomization is stratified by the screening CS dose and screening 
SLEDAI-2K score, and region in order to balance subjects equally across treatment groups based 
on these characteristics, which may indicate the background severity of disease and/or background 
level of disease control and will also balance for potential regional differences in SLE background 
medication.
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5
STUDY POPULATION
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
All screening and randomization evaluations must be completed and reviewed to confirm that
potential subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for screening 
failure, as applicable. CRS and the PRA medical monitor will review all eligibility criteria for all 
subjects who are not initially screen-failed by the site. Study designated therapeutic experts outside 
of the Sponsor and CRO may review eligibility criteria as needed. No subject will be randomized 
without confirmation of eligibility by CRS and the PRA medical monitor. In addition, 
 will 
assign BILAG grades for all subjects based on information provided by the sites. Procedures 
conducted as part of the subject’s routine clinical management and obtained before signing of 
informed consent may be utilized for screening purposes, provided the procedure meets the 
protocol-defined criteria and has been performed within the timeframe defined in the Schedules of 
Activities (Section 1.3). However, all laboratory testing must be performed by the study-specific 
central laboratory.
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The duration of the screening period (SP) is up to 4 weeks. If eligibility parameters cannot be 
obtained within this time period, the SP may be extended by up to 5 days if approved by the 
medical monitor. Rules for retesting and rescreening are provided in Section 5.5.
To be eligible for the study, subjects must meet the criteria in Section 5.1. To be randomized into 
the study on Day 1, subjects must meet the criteria in Section 5.3.
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) Willing to participate in the study and have the ability to give informed consent 
b) Willing and able to complete all study-specific procedures and visits
2) SLE Disease Characteristics
a) Diagnosed ≥24 weeks before the screening visit
b) Meets the Systemic Lupus International Collaborating Clinics (SLICC) classification 
criteria for SLE9 APPENDIX 5
c) One of the following: elevated antinuclear antibodies (ANA) ≥1:80 or positive 
anti-dsDNA (positive includes indeterminate results) or positive anti-Smith (anti-Sm) as 
determined by the central laboratory
d) Total SLEDAI-2K score ≥6 points and clinical SLEDAI-2K score ≥4 points with joint 
involvement and/or rash (score must be confirmed by CRS)
i)
Lupus headache, alopecia, organic brain syndrome, and mucosal ulcers cannot count 
toward the points required for screening at entry.
ii) Clinical SLEDAI-2K excludes laboratory abnormalities such as hematuria, pyuria, 
urinary 
casts, 
proteinuria, 
positive 
anti-dsDNA, 
decreased 
complement, 
thrombocytopenia, and leukopenia.
e) At least 1 of the following BILAG-based protocol-specific manifestations of SLE 
 
:
i)
BILAG A or B grade in the Mucocutaneous body system. 
 
 
 
 
ii) Modified BILAG A or B score in the Musculoskeletal body system 
 
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iii) If only 1 B and no A grade is present in the Mucocutaneous body system or in the 
Musculoskeletal body system due to arthritis, then at least 1 B grade must be present 
in one of the other body systems, for a total of 2 BILAG B body system grades.
3) Medications for SLE
a) Background therapy is required for ≥12 weeks before the screening visit and must be at
a
stable dose for ≥8 weeks before the screening visit and remain stable until 
randomization and throughout study participation. Details for specific medications are as
follows:
x
Immunosuppressants (combinations of these are NOT permitted):
o
azathioprine (maximum 200 mg/day)
o
6-mercaptopurine (6-MP)
o
methotrexate (MTX; maximum 25 mg/week; dose and route of administration
of MTX may not be changed for 8 weeks before the screening visit and
throughout study participation)
o
leflunomide
o
mycophenolate mofetil/mycophenolic acid (MMF). Note: Subjects who are
receiving MMF may participate in the study only if administered as a
maintenance therapyand up to a maximum of 2 g/day(or equivalent); in subjects
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TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
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of African ancestry, 3 g/day (or equivalent) is acceptable. Treatment may be
interrupted due to neutropenia per the product label.
x
Antimalarials: chloroquine, hydroxychloroquine, or quinacrine; monotherapy is
permitted if the minimum doses are met: chloroquine 125 mg QD, 
hydroxychloroquine 200 mg QD, or quinacrine 100 mg QD
x
Required discontinuation periods for other immunomodulatory
drugs (eg,
cyclosporine, tacrolimus, etc) or biologic drugs (eg, rituximab, belimumab,
tocilizumab, etc) are provided in APPENDIX 7. If a drug is not specifically listed, 
consult the 
 medical monitor for guidance. Usual discontinuation periods are 
4 weeks or 5 half-lives, whichever is longer.
b) CS (prednisone or equivalent) background therapy is permitted but not required. For 
subjects taking CS, the dose must be stable for ≥2 weeks before the screening visit, 
cannot exceed 30 mg/day at screening, and must remain stable until randomization. 
CS monotherapy is not permitted. Prednisone equivalents are provided in APPENDIX 6.
c) Requirements for subjects who are receiving chronic therapy with nonsteroidal 
anti-inflammatory drugs (NSAIDs; including marketed cyclooxygenase-2 inhibitors) are 
as follows; exceptions or changes may be possible with approval by the 
 medical 
monitor:
x
Doses must be stable for 14 days before the screening visit and must remain stable 
until randomization and throughout the study.
x
No more than 1 oral NSAID may be used (at a stable dose) during the study and 
may be combined with topical NSAIDs.
x
Use of 1 or more topical NSAIDs is permitted but must follow a stable regimen 
throughout the study.
x
Aspirin is allowed (in addition to a single NSAID and topical NSAIDs) at stable 
doses no higher than 325 mg/day throughout the study.
4) Age and Reproductive Status
a) Men and women aged 18 to 75 years inclusive at the time of screening
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic 
gonadotropin [β-HCG]) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding.
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d) WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study treatment(s) (BMS-986165 or placebo) plus 5 half-lives of study 
treatment (3 days) plus 30 days (duration of ovulatory cycle) for a total of 33 days post 
treatment completion.
e) WOCBP who are continuously not heterosexually active are exempt from contraceptive 
requirements and still must undergo pregnancy testing as described in this section.
f)
Investigators shall counsel WOCBP and men 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).
g) Men 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 or placebo). 
h) Azoospermic males are exempt from contraceptive requirements. 
i)
N/A per Revised Global Protocol im011021-revprot04
5.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study:
1) Target Disease Exceptions
a) Drug-induced SLE
b) Subjects with other autoimmune diseases (eg, multiple sclerosis, psoriasis, IBD, etc) are 
excluded. Subjects with type I autoimmune diabetes mellitus, thyroid autoimmune disease, 
Celiac disease, or secondary Sjögren’s syndrome are not excluded.
c) Subjects with SLE overlap syndromes such as scleroderma and mixed connective tissue 
disease are excluded. Subjects with an overlap syndrome of SLE with rheumatoid arthritis
are not excluded as long as they meet the criteria for the classification of SLE as outlined 
in the inclusion criteria (Section 5.1, Inclusion Criterion 2).
d) Subjects with antiphospholipid antibody syndrome on stable anticoagulant therapy at an 
effective dose (eg, if on warfarin, an international normalized ratio [INR] target 2 to 3 or 
as appropriate for the clinical situation) are allowed if this is not the sole or the predominant 
feature of their SLE. Subjects with a serious thrombotic event (eg, pulmonary embolism, 
stroke, deep vein thrombosis) or unexplained pregnancy loss within 1 year before the 
screening visit are excluded. Subjects with a history of catastrophic antiphospholipid 
syndrome or saddle embolism are excluded. Subjects with a history of 3 or more 
unexplained consecutive pregnancy losses would also be excluded.
e) Subjects with active or unstable lupus neuropsychiatric manifestations, including but not 
limited to any condition defined by BILAG A criteria are excluded, with the exception of 
subjects with mononeuritis multiplex and polyneuropathy, who are allowed.
f)
Subjects with active, severe lupus nephritis (World Health Organization Class III, IV) that 
requires or may require treatment with cytotoxic agents or high-dose CS are excluded.
Subjects with prior, controlled renal disease with serum creatinine ≤2× upper limit of 
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normal (ULN) and either residual proteinuria up to 3 g/day or a urine protein/creatinine 
ratio (UPCR) of 3 mg/mg or 339 mg/mmol are allowed. Control of renal disease must be 
documented with at least 2 measurements of proteinuria or UPCR over the past 6 months.
2) Other Medical Conditions and History
a) Women who are pregnant or breastfeeding
b) Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, 
hematologic, gastrointestinal, endocrine, pulmonary, immunologic, psychiatric) or local 
active infection/infectious illness that, as determined by medical judgment, will 
substantially increase the risk to the subject if he or she participates in the study
c) Any major surgery within the last 30 days before the first dose of study treatment, or any 
surgery planned during the course of the study
d) Cancer or history of cancer or lymphoproliferative disease within the previous 5 years 
(other than adequately treated cutaneous basal cell or squamous cell carcinoma with no 
evidence of recurrence)
e) Class III or IV congestive heart failure as defined by the New York Heart Association
(NYHA) or any recent onset of heart failure resulting in NYHA Class III/IV symptoms
f)
Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and/or any 
history of significant cerebrovascular disease within 24 weeks before screening
g) Current or recent (within 3 months before randomization) gastrointestinal disease, 
including gastrointestinal surgery, that could impact the absorption of study treatment
h) Subject with non-SLE concomitant illness, as determined by medical judgment, who is 
likely to require additional systemic glucocorticosteroid therapy during the study (eg, 
asthma).
i)
Significant blood loss (> 500 mL) or blood transfusion within 4 weeks before 
randomization
j)
Inability to take medication orally
k) Inability to undergo venipuncture and/or tolerate venous access
l)
Recent (within 6 months before randomization) drug or alcohol abuse as defined by the 
Diagnostic Criteria for Drug and Alcohol Abuse in the Diagnostic and Statistical Manual 
of Mental Disorders IV (APPENDIX 8)
m) Any other sound medical, psychiatric, and/or social reason as determined by medical 
judgment
3) Prior and Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments (Section 6.7.1); inability to 
comply with discontinuation requirements listed in APPENDIX 7
b) Taking more than 1 immunosuppressant
c) Prior exposure to TYK2 inhibitors
d) Prior exposure to anifrolumab, rontalizumab, ustekinumab, or interferon alpha kinoid 
(INFα Kinoid)
e) Current administration of opioids unless all the following criteria are met:
i)
The prescribed dose has been stable for ≥4 weeks before screening
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ii) The drug is not used on an as-needed basis
iii) The dose is expected to remain stable through the study period
iv) In the opinion of the investigator, the subject’s use of opioids will not impact the
protocol-specific efficacy and safety assessments
v) The dose does not exceed the equivalent of 30 mg of morphine per day (see
APPENDIX 18 for morphine milligram equivalents of commonly used opioids)
f)
Other investigational agents must be discontinued at least 12 weeks or 5 half-lives before 
screening, whichever is longer
4) Findings Related to Possible Infection
a) Evidence of active or latent tuberculosis (TB), as follows:
xPositive chest X-ray for evidence of active pulmonary TB within 6 months before 
screening
xSubjects with negative chest X-ray within 6 months before screening may be 
eligible provided any of the following apply:
o
negative IFN gamma release assay (IGRA)
o
positive IGRA and no symptoms of active TB, and have previously 
(within 5 years) received adequate documented treatment for latent TB, 
per investigator’s medical judgment
o
positive IGRA and no symptoms of active TB, but have NOT previously 
(within 5 years) received adequate documented treatment, per 
investigator’s medical judgment; subject must initiate prophylactic 
treatment per local guidelines and may rescreen after 1 month of 
treatment (if subject is enrolled, the prophylactic TB treatment must 
continue throughout the study)
o
indeterminate IGRA at screening with no signs or symptoms of active 
TB must be retested for confirmation. If the second test is again 
indeterminate, the subject will be excluded from the study. If the retest 
is positive, the subject should be treated as having latent TB infection.
If the retest is negative, subject may be eligible, provided no other 
exclusion criteria for TB is met
b) Hepatitis C, hepatitis B, or human immunodeficiency virus (HIV) infection as 
demonstrated by a positive blood screen for hepatitis C antibody (anti-HCV), hepatitis B 
surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or HIV-1 and -2 antibody. 
Subjects who have been vaccinated for hepatitis B (hepatitis B surface antibody 
[anti-HBs]-positive) are not excluded. Note that anti-HBs is not requested (APPENDIX 9).
Note: Subjects who are newly found to be HIV-positive should be directed to appropriate 
follow-up care.
c) Currently on any therapy for chronic infection (eg, pneumocystis, cytomegalovirus, herpes 
simplex, herpes zoster, invasive bacterial or fungal infections, or atypical mycobacteria)
d) History of congenital or acquired immunodeficiency
e) Known active infection, or any major episode of infection requiring hospitalization or 
treatment with parenteral (intramuscular or IV) antimicrobial agents (eg, antibiotics, 
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antiviral, antifungal, or antiparasitic agents) within 30 days of randomization, or 
completion of oral antimicrobial agents within 2 weeks of randomization
f)
Previous history of herpes zoster, herpes simplex, or influenza infection within 12 weeks 
before randomization or a history of disseminated/complicated herpes zoster infection 
(multidermatomal involvement, ophthalmic zoster, central nervous system involvement, or 
post-herpetic neuralgia)
g) Administration of a live vaccine within 90 days or an inactivated vaccine within 30 days 
before randomization. Heat-killed or otherwise inactivated or protein vaccines (eg, 
influenza and pneumococcal vaccines) may be received at any time on study. Furthermore, 
live vaccines should not be used during treatment or within the 2 months following last 
dose, and any other inactivated vaccines (eg, tetanus, etc) should be used according to local 
guidelines during the TP.
5) Physical and Laboratory Test Findings
a) Clinically significant abnormalities on chest X-ray or ECG
b) Clinically significant abnormalities in laboratory tests including the following:
i)
Serum alanine aminotransferase (ALT) > 2× ULN, unless explicitly related to SLE
ii) Serum aspartate aminotransferase (AST) > 2× ULN, unless explicitly related to SLE
iii) Serum total bilirubin > 1.5× ULN, unless explicitly related to SLE or documented 
Gilbert's syndrome 
iv) Hemoglobin < 8 g/dL (80 g/L) or, if due to hemolytic anemia related to SLE, < 7 g/dL
(70 g/L)
v) Proteinuria > 3.0 g/day (3000 mg/day) or equivalent level of proteinuria as assessed 
by UCPR (3 mg/mg or 339 mg/mmol)
vi) Estimated glomerular filtration rate < 30 mL/min
vii)Absolute white blood cell count < 1.2× 103/μL (1.2× 109/L)
viii)Platelet count < 50 × 103/μL (50 × 109/L)
ix) Abnormal free thyroxine (T4) (if the thyroid-stimulating hormone [TSH] is abnormal 
at screening, a free T4 will be assessed; subjects with abnormal TSH and abnormal 
free T4 will be excluded but after discussion with the 
 medical monitor may be 
able to rescreen a minimum of 6 weeks after adjustment of thyroid hormone 
replacement therapy).
c) Any other significant laboratory or procedure abnormalities, as determined by medical 
judgment, that might pose unacceptable risk to the subject during the study
6) Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to continue 
as a subject. Strict conditions apply and BMS approval is required).
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
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c) Inability to comply with the study protocol
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
5.3
Randomization
Eligible subjects must meet the following criteria on Day 1 before randomization and the first 
dose:
1. The subject continues to satisfy all eligibility criteria.
2. If the subject had rash at screening, the subject must have a total score of the erythema and 
scale components (excluding mucous membrane ulcerations and nonscarring alopecia) of the 
CLASI disease activity score of ≥3.
3. If the subject had moderate or severe arthritis at screening, the inclusion criteria for 
BILAG-based protocol-specific manifestations of SLE in Section 5.1, Inclusion Criterion 2)e) 
must continue to be met.
5.4
Lifestyle Restrictions
No restrictions are required. However, general skin care measures are recommended that are 
standard for patients with SLE, 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.
Study treatment may be taken without regard to meals. However, subjects are required to fast for 
a minimum of 10 hours before visits on which fasting lipid and fasting glucose samples will be 
drawn (at 2 of these visits [Days 1 and 85], fasting PK samples will also be drawn).
5.5
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently randomized in the study for any reason. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure subjects, to meet the Consolidated 
Standards of Reporting Trials publishing requirements, and to respond to queries from regulatory 
authorities. Minimal information includes date of consent, demography, screen failure details, 
eligibility criteria, and any serious AEs.
5.5.1
Retesting During Screening Period; Rescreening
For laboratory parameters and/or assessments that initially do not meet eligibility requirements, a 
single retest within the 28-day SP is permitted in an effort to find all possible well-qualified 
subjects. Consultation with the 
 medical monitor may be needed to identify whether repeat 
testing of any particular parameter is clinically relevant.
The study permits the rescreening (after the end of the initial 4-week SP) of a subject who 
discontinues the study as a pretreatment failure (ie, the subject fails screening or randomization 
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and has not been treated). The subject must be reconsented and will be assigned a new 
identification number, and a full screening visit must be performed again. Other than exceptional 
circumstances which must be reviewed and approved by the medical monitor, a subject can only 
be rescreened 1 time. Depending on the timing of rescreening, repetition of some assessments may 
not be required. Duration of existing treatments and required discontinuation periods shall be 
considered relative to the given screening visit and/or randomization.
The most current result prior to randomization is the value by which study inclusion will be 
assessed, as it represents the subject’s most current clinical state.
6
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device intended to be administered to a study subject according to the study randomization 
or treatment allocation
Study treatment includes both investigational [medicinal] product (IP/IMP) and noninvestigational 
[medicinal] product (non-IP/non-IMP) and can consist of BMS-986165 and placebo. Information 
about the pharmacology and previous experience with BMS-986165 is provided in Section 2.2.
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 preventative, diagnostic, or 
therapeutic reasons, as components of the standard of care for a given diagnosis, may be 
considered as noninvestigational products.
Table 5
shows the study treatments for 
Protocol IM011021.
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Table 5: Study Treatments for IM011021
Product 
Description/Class and 
Dosage Form
Potency
IP/Non-IP
Blinded/Open
-Label
Packaging/
Appearance
Storage Conditions 
(per label)
Comments
BMS-986165 oral capsule
(as the free 
base)
IP
Blinded
Blister card containing 
64 active
(3 mg BMS 986165) 
and/or placebo capsules 
to equal required daily 
dosing
Store at 2°C to 8°C (36°F 
to 46°F). Store in original 
container.
Placebo matching BMS-
986165 oral capsule
Not applicable
IP
Blinded
Blister card containing 
64 active
(3 mg BMS-986165) 
and/or placebo capsules 
to equal required daily 
dosing
Store at 2°C to 8°C (36°F 
to 46°F). Store in original 
container.
Any of the following: 
AZA, 6-MP, MTX, 
leflunomide, MMF; 
chloroquine, 
hydroxychloroquine, 
quinacrine
As prescribed
Non-IP
Open-label
As provided
As indicated
Subjects are to be receiving at least 1 of these 
at a stable dose for ≥8 weeks before the 
screening visit, throughout the screening 
period, and throughout the study. See 
Inclusion 3a (Section 5.1) for further 
information. Non-IP will not be provided by 
the Sponsor.
CS: prednisone (or 
equivalent)
≤30 mg/day
(or equivalent)
Non-IP
Open-label
As provided
As indicated
CS is not required; if on CS, the dose must be 
stable for ≥2 weeks before the screening 
visit, and throughout the SP. A dose up to 
30 mg/day prednisone or equivalent is 
permitted at the screening visit (see Inclusion 
3b in Section 5.1) and should be tapered 
according to the protocol guidelines during 
the treatment period. Information about CS 
tapering 
 is provided in 
Sections 6.7.3
6-MP = 6-mercaptopurine; AZA = azathioprine, CS = corticosteroid; IMP = investigational medicinal product; IP = investigational product; MMF = mycophenolate 
mofetil/mycophenolic acid; MTX = methotrexate; SP = screening period
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6.1
Treatments Administered
Dose information for each treatment group for the TP is provided in Table 6. Study treatment will 
be supplied in blister card kits. The capsules will be arranged into sets to be taken in the morning 
and in the evening, approximately 12 hours apart. 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.
Table 6: 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
3 mg
4 active capsules QD in the morning; and 
4 placebo capsules QD in the evening
Oral
6 mg BID 
BMS-986165
3 mg
2 active and 2 placebo capsules; BID
Oral
3 mg BID 
BMS-986165
3 mg
1 active and 3 placebo capsules; BID
Oral
Placebo
Not applicable
4 placebo capsules; BID
Oral
BID = twice daily; QD = once daily
6.2
Method of Treatment Assignment
At the time of the screening visit, immediately after informed consent is obtained and before any 
study-related procedures are performed, the investigative site will access the enrollment option 
using IRT for assignment of a subject number (including subjects not subsequently randomized or 
treated). This number will be unique across all sites. Enrolled subjects, including those not dosed, 
will be assigned sequential subject numbers. The subject number may not be used for any other 
subject. If a potential subject is rescreened, they will be given a new identification number.
CRS and the PRA medical monitor will confirm subject eligibility based on criteria in Section 5.
Eligible subjects will be centrally randomized using IRT to receive oral treatment with 
BMS-986165 12 mg QD, 6 mg BID, 3 mg BID, or placebo BID according to a computer-generated 
block randomization scheme and in accordance with stratification criteria. Randomization 
numbers will be assigned prior to dosing.
Before the study is initiated, each user (at investigative sites) will receive log-in information and 
directions on how to access the IRT. Study treatment will be dispensed at study visits as shown in 
Section 1.3 (Schedules of Activities).
6.3
Blinding
6.3.1
Maintaining the Blind
Blinded treatment assignments will be managed using IRT. All capsules (BMS-986165 3 mg and 
placebo) are identical in appearance, and they will be supplied in blister packs with each daily dose 
made up of the appropriate combination of active and/or placebo capsules to provide the correct 
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treatment (as shown in Table 6). Investigative site staff, Sponsor and designee personnel, the 
 
(Section 4.1.1), and subjects and their families will remain blinded to treatment assignments. 
Blinding of treatment assignment is critical to the integrity of this clinical study. 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.
For information on how to unblind in an emergency, consult the IRT manual.
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 study 
director. The method of unblinding for emergency purposes is described in the IRT manual. 
Subject 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. Any request to 
unblind a subject for nonemergency purposes must be discussed with the 
 medical monitor 
prior to unblinding.
Designated staff of Bristol-Myers Squibb Research & Development (or designee) may be 
unblinded (obtain the randomization codes) prior to database lock to facilitate the bioanalytical 
analysis of pharmacokinetic samples. 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.
6.4
Dosage Modification
There is no provision for dose modification of study treatment. Titration of CS and its use as rescue 
therapy are discussed in Section 6.7.3
. Modification of other background SLE therapies 
or dose regimens is not permitted during study participation. Subjects should continue to take their 
assigned treatment even if they experience flares and/or are unable to taper their CS dose, unless 
any of the criteria in Section 7.1 are met.
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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 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 study treatment is stored in accordance with the environmental conditions (temperature, light, 
and humidity) required by 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.
Investigational product 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).
Further guidance and information for final disposition of unused study treatment are provided in 
APPENDIX 1.
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 capsules 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 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
All medications ever taken for SLE including topical, discontinued, and investigational therapies 
must be recorded; medications with dose changes may record the overall dates with last dose used. 
All medications taken from within 4 weeks before screening until 30 days after the last dose of 
study treatment (inclusive) must be recorded on the eCRF. Other than existing treatment for SLE 
(with restrictions as described in the eligibility criteria [Section 5.1]), concomitant medications 
(prescription, over-the-counter [OTC], or herbal) should only be administered during the study if 
they are prescribed for treatment of specific clinical events.
6.7.1
Prohibited and/or Restricted Treatments
Restrictions and prohibitions on prior and concomitant medications are as follows:
1. Prior exposure to BMS-986165 or other TYK2 inhibitors is prohibited.
2. Rescue therapy other than prednisone or equivalent is prohibited.
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3. Use of intramuscular, intra-articular, intrabursal, and IV CS is prohibited (Inclusion
Criterion 3)b); Section 5.1). Initiation during the study of short-term treatment with inhaled
CS for a nonlupus medical condition must be discussed with the
 medical monitor. Topical
CS use may not be initiated during treatment. Modified-release CS formulations are prohibited.
4. Topical NSAID use may not be initiated during treatment. No more than 1 oral NSAID may
be used during the study. Aspirin is allowed (in addition to a single NSAID and topical
NSAIDs) at stable doses no higher than 325 mg/day throughout the study. NSAIDs may not
be used on an as-needed basis. Although regimens are required to be stable throughout the
study, NSAID dosing may be decreased or discontinued if due to NSAID toxicity. Adjustments
in NSAID regimens must be discussed with the 
 medical monitor.
5. Use of opioid analgesics is prohibited unless criteria outlined in Exclusion Criterion 3)e);
Section 5.2, are met.
6. Use of cyclophosphamide (including ophthalmic) or any IV, intrabursal, intratendinous sheath,
intramuscular, subcutaneous, intra-articular, or biologic agent is prohibited. Required
discontinuation periods for immunomodulatory and biologic drugs before the signing of
informed consent are provided in APPENDIX 7. For similar agents not listed, the
discontinuation period is 4 weeks or 5 half-lives, whichever is longer, and must be discussed
with the 
 medical monitor.
7. Live vaccines are prohibited during the TP or within the 2 months after the last dose.
Heat-killed or otherwise inactivated or protein vaccines such as influenza 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 during the TP (Exclusion Criterion 4)g);
Section 5.2).
8. Exposure to any investigational drug or placebo within 12 weeks or 5 half-lives (whichever is
longer) before screening is prohibited (Exclusion Criterion 3)f); Section 5.2)
9. Use of any other drugs, including OTC medications and herbal preparations, within 1 week
before the first dose of study treatment is prohibited, except medications cleared by the 
medical monitor
6.7.2
Existing Therapies for Systemic Lupus Erythematosus
All subjects will continue their existing SLE treatment(s) during the study (if the treatment 
complies with the eligibility criteria; Section 5). The dose and regimen of background SLE 
treatments must not change during study participation. Details of permissible therapies are as 
follows:
x
At least 1 background agent as specified in Inclusion Criterion 3)a) (Section 5.1); use of more
than 1 immunosuppressant in combination is NOT permitted.
x
CS therapy with prednisone or equivalent as specified in Inclusion Criterion 3)b) (Section 5.1);
see restrictions in Section 6.7.1. CS tapering 
 are described in
Sections 6.7.3
x
Chronic NSAID therapy as specified in Inclusion Criterion 3)c) (Section 5.1)
x
Stable preexisting topical CS therapy as specified in Inclusion 3)b) (Section 5.1)
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6.7.3
Corticosteroid Tapering
For subjects receiving prednisone or equivalent, the dose of CS must be stable for 2 weeks before 
the screening visit (signing of informed consent) and throughout the SP until randomization. Up 
to 30 mg/day prednisone or equivalent is permitted during the SP (and for the preceding 2 weeks). 
Rules for CS tapering are as follows:
x
Tapering of CS may begin at any time after the first dose of IP on Day 1.
x
For subjects receiving > 7.5 mg/day prednisone or equivalent, tapering must start by 
Week 8.
x
For all subjects, the CS dose must be ≤7.5 mg prednisone or equivalent by Week 20 (if 
this is not possible, the subject will remain on treatment, but will be a nonresponder for 
analysis purposes).
x
Investigators must assess the subject’s suitability for CS taper at each visit (taper is not 
required to start until Week 8), and the last day for CS taper is the Week 20 visit.
x
The CS dose must be tapered (beginning by Week 8 and continuing until the Week 20 visit) 
unless any of the following are observed:
o
New or worse BILAG or SLEDAI-2K activity for any of the following parameters: 
central nervous system, vasculitis, myositis, cardiorespiratory, gastrointestinal, 
ophthalmologic, renal, or thrombocytopenia
o
New or worsening hemolytic anemia
o
CLASI activity score ≥10
o
Active joint count of 8 or more joints with both tenderness AND swelling
x
Tapering is required if disease activity has not worsened. The investigator must justify any 
decision not to taper. Criteria met or not met for taper will be documented on the eCRF at 
each appropriate visit.
x
The CS dose must remain stable from Week 20 until Week 32. Tapering may be resumed 
at the Week 32 visit according to the same parameters as earlier in the study. The last day 
for CS taper is the Week 40 visit, and the CS dose must remain stable from Week 40 until 
Week 48.
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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. In addition, for subjects who continue to 
demonstrate clinical benefit and who elect to enroll, BMS will continue to provide study treatment 
via Protocol IM011074, which is an LTE of the current study. Participation in IM011074 is not 
required for participation in this study, however.
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 the IP (and non-IP at the discretion of the investigator) for any of the 
following reasons:
x
A 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
x
Any clinical AE, laboratory abnormality, or intercurrent illness that, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of 
the subject
x
Termination of the study or a specific dose group (for subjects receiving that dose) by BMS
x
Loss of ability to freely provide consent through imprisonment or involuntary incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness
x
Unblinding of a subject’s treatment assignment for any reason (emergency or 
nonemergency)
x
Pregnancy
x
Abnormal liver tests suggestive of drug-induced liver injury (DILI) as defined in 
Section 8.3.8 or if the investigator believes that it is in the best interest of the subject.
Refer to the Schedules of Activities (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.
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In the case of pregnancy, the investigator must immediately notify the 
 medical monitor or 
designee of this event. In the event a normal healthy female subject becomes pregnant during a 
clinical trial, the study treatment must be discontinued immediately. In most cases, the study 
treatment will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for subject safety). Please call the 
 medical monitor within 24 hours of awareness 
of the pregnancy. If the investigator determines a possible favorable benefit/risk ratio that warrants 
continuation of study treatment, a discussion between the investigator and the 
 medical 
monitor must occur.
All subjects who discontinue study treatment should comply with protocol-specified follow-up 
procedures as outlined in Section 1.3. 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). Subject replacement 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.
Subjects who discontinue study treatment will remain in the study for continued follow-up.
7.2
Discontinuation from the Study
Subjects who request to discontinue study treatment (possible circumstances are listed in 
Section 7.1) 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. 
x
Subjects should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.
x
The withdrawal of consent should be explained in detail in the medical records by the 
investigator and entered on the appropriate eCRF page.
x
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.
x
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
Post Study Treatment Follow-Up
In this study, the proportion of subjects who achieve BICLA response at Week 32 after treatment 
with BMS-986165 or placebo is a key endpoint of the study. 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 
 survival 
follow-up data as required and in line with Section 3 until death or the conclusion of the study. 
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7.4
Lost to Follow-Up
x
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.
x
Lost to follow-up is defined by the inability to reach the subject after a minimum of 
3 documented phone calls, faxes, or emails as well as lack of response by subject to 
1 registered mail letter. All attempts should be documented in the subject’s medical 
records.
x
If it is determined that the subject has died, the site will use permissible local methods to 
obtain date and cause of death.
x
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. 
x
The site staff and representative will consult publicly available sources, such as public 
health registries and databases, to obtain updated contact information.
x
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.
7.5
Replacement of Subjects
Subject replacement is not permitted.
8
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and timing are summarized in the Schedules of Activities (Section 1.3). Waivers 
or exemptions from protocol-required evaluations are not allowed.
8.1
Efficacy Assessments
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.
Baseline assessments must be performed per protocol (standard of care assessments may not be 
used for baseline). 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.
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Note: NSAIDs must be withheld for at least 12 hours before visits at which BILAG, SLEDAI-2K,
joint counts, CLASI, or Physician’s Global Assessment of Disease Activity are assessed (ie, all 
scheduled visits). Study treatment must not be taken on visit days until after efficacy assessments.
The following procedures or tools will be used to assess subjects’ SLE disease activity during the 
study (see schedule in Section 1.3):
x
BILAG-200410, 11, 12, 13 (APPENDIX 10): 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, 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).
x
SLEDAI-2K 14,15 (APPENDIX 11): The SLEDAI-2K is a global index based on weighted 
scores for each of 24 clinical findings rated as present or absent at the time of the visit or in the 
last 30 days. The SLEDAI-2K assigns relative weights to each parameter.
x
CLASI 16,17 (APPENDIX 12): The CLASI assesses cutaneous disease activity by body surface 
area; 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.
x
40-joint count: A 40-joint count is used. This 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).18, 19, 20 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.
x
Physician’s Global Assessment of Disease Activity assessed using a 3-point visual analog scale 
(VAS).
The following composite measures will be determined based on some of the assessments described 
above:
x
BICLA response21 as defined in Section 9.3.1.1
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x
SLE Responder Index22 (SRI): The SRI is a composite endpoint that defines a responder as a 
patient whose disease course fulfills all of the following:
o
A predefined reduction (number of points) from baseline in SLEDAI-2K score14,15
(APPENDIX 11). The SRI can be calculated based on the number of points of reduction in 
the SLEDAI-2K (SRI[4], SRI[5], SRI[6], and SRI[7]).
o
No new BILAG A (severe disease activity) or not more than 1 new BILAG B (moderate 
disease activity) organ domain grade
o
No worsening from baseline in the Physician’s Global Assessment of Disease Activity 
scale by more than 0.3 points
x
Lupus Low Disease Activity State (LLDAS):23,24
LLDAS 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.
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8.2
Laboratory Assessments Related to SLE Disease Activity
The following laboratory tests will be performed according to the schedule in Section 1.3 to gather 
more information about SLE disease activity: Coomb’s test (direct); serum complement (C3, C4); 
quantitative immunoglobulins (IgG, IgA, IgM); anti-dsDNA; anti-Sm; ANA; anti-Ro (SSA); 
anti- La (SSB); anti-ribonucleoprotein (RNP); T cells, B cells, and natural killer cells (TBNK); 
and high-sensitivity C-reactive protein. Laboratory assessments that are used in some efficacy 
assessments (eg, BILAG and SLEDAI-2K), such as complete blood count and renal function tests, 
are also used for safety assessments and are described in Section 8.5.3. 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.
8.3
Adverse Events
Adverse events 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 serious adverse event (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.
The definitions of an AE or SAE can be found in APPENDIX 3.
Contacts for SAE reporting are specified in Appendix 3.
The event (term), along with its start and stop dates, maximum intensity (mild, moderate, or 
severe), seriousness (yes/no), relationship to the IP (yes/no), action taken with regard to the IP, 
and outcome will be recorded in the eCRF.
8.3.1
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. Adverse events of interest 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 may be collected on the eCRF in order to better characterize and 
understand them.
8.3.2
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE information should begin at initiation of study treatment and 
continue until the last follow-up visit, at the timepoints specified in the Schedules of Activities 
(Section 1.3).
The Reference Safety Information in Sections 5.6.1 and 5.6.2 of the IB should be used to determine 
the expectedness of SAEs for expedited reporting. Following the subject’s written consent to 
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participate in the study, all SAEs, whether related or not related to study treatment, must be 
collected, including those thought to be associated with protocol-specified procedures.
All SAEs that occur from the time the informed consent form (ICF) is signed through 30 days after 
the final dose of the study treatment must be reported to 
 Drug Safety. After that time, only 
SAEs deemed by the investigator to be related to the study treatment or a study procedure should 
be reported.
x
The investigator must report any SAE that occurs after these time periods and that is believed 
to be related to study treatment 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 eCRF.
x
All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in APPENDIX 3.
x
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.
8.3.3
Method of Detecting AEs and SAEs
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. To prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs. Adverse events will be reported 
by the subject (or, when appropriate, by a caregiver, surrogate, or the subject’s legally authorized 
representative). Nonserious SLE-related AEs will be collected only on the disease assessment 
instruments and not reported as AEs.
All AEs and SAEs that arise in the study will be reported and investigated. However, because of 
the characteristics of the disease under study and of BMS-986165 itself, subjects will be more 
closely monitored for signs of infection and for treatment-emergent rash (Section 8.3.9).
8.3.4
Follow-up of AEs and SAEs
x
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if
they become serious (see APPENDIX 3).
x
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.
x
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 
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skin reactions and 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 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 7.4).
Further information on follow-up procedures is given in APPENDIX 3.
8.3.5
Regulatory Reporting Requirements for SAEs
x
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.
x
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 institutional review board (IRB)/independent ethics 
committee (IEC), if appropriate according to local requirements.
The Sponsor or 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 Code of Federal Regulations 21 CFR Parts 312 and 320. Suspected, unexpected 
serious adverse reactions are a subset of SAEs and will be reported to the appropriate regulatory 
authorities and investigators following local and global guidelines and requirements.
8.3.6
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a subject is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration, the investigator must immediately notify 
 Drug 
Safety of this event and complete and forward a Pregnancy Surveillance Form to 
 Drug Safety
within 24 hours of awareness of the event and in accordance with SAE reporting procedures 
described in APPENDIX 3.
In most cases, the study treatment will be permanently discontinued in an appropriate manner (eg, 
dose tapering if necessary for subject safety).
Any pregnancy that occurs in a female partner of a male study subject should be reported to 
 
Drug Safety. 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.
Protocol-required procedures for study discontinuation and follow-up must be performed on
subjects who become pregnant.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
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8.3.7
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or electronic SAE Report Form, as appropriate. Paper forms are only intended as a back-up
option when the electronic system is not functioning.
x
Any laboratory test result that is clinically significant or meets the definition of an SAE 
x
Any laboratory test result abnormality that required the subject to have study treatment 
discontinued or interrupted
x
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 versus low hemoglobin value).
8.3.8
Potential Drug-Induced Liver Injury
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see APPENDIX 3 for reporting details).
Potential DILI is defined by presence of all of the following characteristics:
x
ALT or AST elevation > 3× ULN
x
total bilirubin > 2× ULN, without initial findings of cholestasis (elevated serum alkaline
phosphatase)
x
no other immediately apparent possible causes of AST or AST 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
8.3.9
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, X-ray 
filming, 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.
8.4
Overdose
For this study, any dose of blinded study treatment that is more than 2-days’ worth of study 
treatment within a 24-hour time period will be considered an overdose. 
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 until BMS-986165 
can no longer be detected systemically (at least 3 days).
3. Document the quantity of the excess dose as well as the duration of the overdosing in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the 
 medical monitor based on the clinical evaluation of the subject.
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8.5
Safety
Planned timepoints for all safety assessments are listed in the Schedules of Activities
(Section 1.3). All urgent safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue treatment.
Safety evaluations that will be performed in addition to AE monitoring are physical examinations 
(PE; Section 8.5.1), TB screening (Section 8.5.2), vital signs, ECGs, concomitant medication 
use, and laboratory tests (Section 8.5.3).
8.5.1
Physical Examinations
Schedules for PEs are provided in Section 1.3. Complete and/or targeted PEs may be performed 
by a Doctor of Medicine (MD), or someone who is authorized to perform the examinations by 
training and has been delegated this task by the principal investigator. While the targeted 
examination may not be as comprehensive as the initial full examination, key aspects should 
evaluate important body systems as clinically indicated. These body systems can include lymph 
nodes, liver, spleen, and breast at the discretion of the examiner. A targeted examination may note 
any changes in the subject’s condition (body systems) since the last assessment and does not 
preclude examination of any of the other body systems as clinically indicated. Every effort should 
be made to ensure the same evaluator will complete the examination for each subject at all visits 
throughout the study. Documentation of who performed the examination is to be recorded in source 
notes.
8.5.2
Tuberculosis Screening and Chest X-ray
A chest X-ray and PE are part of the process to assess a subject’s eligibility as defined in 
Section 5.2, Exclusion Criterion 4a, and outlined in Section 1.3. A chest X-ray at the screening 
visit is required if not already performed within 6 months of obtaining written informed consent.
In addition to a complete PE and medical history to evaluate exposure to TB, all subjects will have 
a screening test, an IGRA (eg, T-spot® or QuantiFERON®), preferably performed centrally. If 
unable to obtain central laboratory results (eg, repeated test due to indeterminate result), an IGRA 
test could be obtained locally, after consultation with the 
 medical monitor.
8.5.3
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 8.3.7). 
Results of clinical laboratory tests performed during screening must be available prior to 
randomization. Additional safety assessments may be performed at local laboratories at the 
investigator’s discretion. The laboratory parameters to be assessed are as follows:
x
Hematology: hemoglobin, hematocrit, total leukocyte count (including differential), 
platelet count, RBC count, and manual differential (separate smear)
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x
Chemistry: AST, ALT, gamma glutamyltransferase, total bilirubin, direct bilirubin, 
alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, 
fasting glucose, total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, 
magnesium, creatine kinase, creatinine clearance (screening only)
x
Coagulation: prothrombin time, INR, and either partial thromboplastin time or activated 
partial thromboplastin time
x
TSH (screening only)
x
Tests performed after a ≥10-hour fast: lipid panel (total cholesterol, high-density 
lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), plasma 
glucose
x
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
x
Serology to be performed at screening: hepatitis C antibody, HBsAg, anti-HBc, HIV-1 and 
HIV-2 antibody, TB (screening only)
In addition, urine pregnancy testing will be performed for WOCBP, and follicle-stimulating 
hormone will be measured to confirm postmenopausal status (as applicable; at screening only).
8.5.4
Imaging Safety Assessment
Not applicable.
8.6
Pharmacokinetics
The PK of BMS-986165 and metabolites (if applicable) will be derived from plasma concentration 
versus time. 
Plasma samples will be analyzed for BMS-986165 and BMT-153261 by a validated assay. 
Pharmacokinetic samples collected from subjects who receive placebo will not be analyzed. 
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. In addition, plasma 
samples will be archived for potential metabolites 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.
The PK parameters to be assessed include:
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
Ctrough
Trough observed plasma concentration
The area under the concentration-time curve in one dosing interval (AUC[TAU]) will be calculated 
if possible.
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8.6.1
Sampling Schedule
The sampling schedule for the assessment of PK and PD is provided in Table 7. Predose samples 
must be drawn before the dose on all visit days, and after a fast (for Day 1 and Day 85 visits) of at 
least 10 hours. As described in Section 1.3, 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. Further details of blood 
collection and processing are provided to sites in the Study Reference Manual.
Table 7: PK and PD Sampling Schedule for BMS-986165 and BMT-153261
Study Day 
of Sample 
Collection
Event
Time
(Relative To 
Dose) 
Hour: Min
Blood 
Sample 
for PK
Blood 
Sample 
for IRG
Notes
1
predose
00:00
X
X
Samples will be collected after the subject has been 
fasted for ≥ 10 hours (fasting is required for other 
assessments at this visit as well). However, subjects 
may eat after the Hour 2 sample has been collected.
1
00:30
X
1
02:00
X
15
predose
00:00
X
X
29
predose
00:00
X
X
57
predose
00:00
X
X
85
predose
00:00
X
X
Samples will be collected after the subject has been 
fasted for ≥ 10 hours (fasting is required for other 
assessments at this visit as well). However, subjects 
may eat after the Hour 4 sample has been collected.
85
00:30
X
85
02:00
X
X
85
04:00
X
X
85
06:00
X
X
113
predose
00:00
X
141
predose
00:00
X
169
predose
00:00
X
X
197
predose
00:00
X
225
predose
00:00
X
X
An aliquot of collected blood sample will be included 
for potential measurement of concomitant medication.
253
predose
00:00
X
281
predose
00:00
X
309
predose
00:00
X
337
predose
00:00
X
X
IRG = interferon-regulated gene; PD = pharmacodynamic(s); PK = pharmacokinetic(s)
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.
8.6.2
Sampling Windows
It is expected that every effort is made to collect PK samples at the times indicated. However, for 
flexibility in PK sampling, the following windows serve as a guideline for PK sample collection:
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x
Predose samples must be drawn before the morning dose on the visit day.
x
The following windows apply to other samples:
o
±0.25 hour for the 0.5-hour sample
o
±0.5 hour for the 2-hour sample
o
± 1 hour for the 4- and 6-hour samples
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. If samples cannot be taken within the 
specified time window every effort should be made to take a sample as soon as possible. Deviations 
from the sampling windows must be noted in the source documents.
Pharmacodynamic sampling will follow the same time window as PK and will be collected at 
matched PK timepoints.
8.7
Supplemental Assessments: Photography
Sites will be equipped with clinical photography supplies. 
 will use the photographs to assist 
in establishing appropriate use of the CLASI instrument for selected visits. Additionally, the 
photographs will be used to help distinguish a rash related to SLE from a rash arising as a side 
effect of the study treatment. Any photographs may be used as supplemental documentation for 
publications and to increase understanding of cutaneous manifestations of interest. Appropriate 
measures will be applied to ensure subject privacy. Details of study photography are provided in 
the Central Photography Manual. Only subjects who consented to photography will be 
photographed.
8.8
Pharmacogenomics
Not applicable
8.9
Biomarkers
Details of blood and urine collection and processing will be provided to the site in the Study 
Reference Manual. Biomarker samples will generally be collected from all study subjects (with 
the exception of Day 2 or 3 samples). Blood and urine will be collected at the timepoints shown in 
Section 1.3 and in Table 7.
The biomarkers to be assessed currently have no utility for clinical decision making, thus, the 
results for individual subjects will not be shared with either the investigator or the subject; 
however, the aggregated results may be shared. The aggregated results may be published to further 
the understanding of BMS-986165 or lupus; however, individually identifiable patient data will 
not. The end of the study for biomarker samples is defined as up to the maximum allowed in the 
individual ICF documents. Although the analysis of some biomarkers will be performed 
immediately, additional biomarker analysis may be delayed while the initial analysis of the study 
results are interpreted and integrated.
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8.9.1
Predictors of Response
Blood will be collected at the screening visit to assess the level of activity of the Type I IFN 
pathway by measuring the expression of IRGs. In addition, steroid-regulated genes and other gene 
signatures may be assessed. These biomarkers will be used to test for potential differences in
subjects’ response to BMS-986165 and CS treatment.
8.9.2
Pharmacodynamics and Mechanism of Action
The PD effects of BMS-986165 will be assessed based on markers in blood and urine, which will 
be collected at the timepoints shown in Section 1.3 and in Table 7. Serum and plasma samples will 
be collected and analyzed for markers of tissue damage and regeneration, such as markers of 
inflammatory damage to collagen. Samples will be collected predose except for the FP visit. 
Samples can also be collected at any time for the Day 2 or 3 sample, which will be collected for a 
subset of subjects for blood ribonucleic acid (RNA) and inflammatory markers (this will be 
performed in a home visit or other means to avoid requiring subjects to return to the site). 
 
 
Lupus is an inflammatory/autoimmune disorder that results in damage to many different tissues. 
It is characterized by elevated expression of the Type I IFN pathway. To assess the effect of 
BMS-986165 on the IFN pathway, blood samples for RNA will be collected to assess the 
expression of IRGs and other genes. 
 
Patients with lupus typically have decreases in complement proteins, C3 and C4, and circulating 
lymphocytes. These will be assessed for evidence of PD activity. Anti-dsDNA will also be 
assessed for PD changes in serum and plasma.
BMS-986165 is expected to inhibit the actions of IL-12 and IL-23. This should result in alterations 
to T-helper cell phenotypes. In addition, B-cell populations are dysregulated in lupus, with 
increases in activated phenotypes. Blood will be collected for lymphocyte profiling including 
assessments of T-helper subpopulations, activated and memory T-cell subpopulations, B-cell 
populations, and dendritic cell populations. These populations will be enumerated in samples from 
a subset of subjects in the USA. In addition, the effects of BMS-986165 on IL-12- and 
IL-23-regulated genes and proteins will also be assessed.
Corticosteroid treatment is common in lupus; however, the effectiveness of this treatment varies 
in different patients. Thus, a broad range of doses are used across patient populations and even 
over time within individual patients. This treatment can confound the interpretation of 
investigational clinical trials. To address this issue, the biological effect of CS use will be assessed 
by measuring a gene signature of CS exposure.
Lupus patients have characteristic alterations in blood cell populations and activation status. Blood 
samples will be collected to assess the numbers and activation status of lymphocyte and leucocyte 
cell subsets.
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9
STATISTICAL CONSIDERATIONS
9.1
Sample Size Determination 
Approximately 360 subjects will be randomized into 1 of 4 treatment arms in a 1:1:1:1 ratio, 
resulting in around 90 subjects per arm. 
 
 
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 With a sample size of 90 subjects per arm, there 
will be at least 84% power to detect a treatment difference of 20% in SRI(4) response rates between 
the BID BMS-986165 treatment arms and placebo
 
 
 
9.2
Populations for Analyses
The following populations are defined for analysis purposes:
Population
Description
Enrolled
All subjects who sign informed consent.
Randomized
All subjects who are randomized to a treatment. Subjects will be 
grouped according to the treatment to which they are randomized 
according to IRT at the start of the TP.
Modified intent-to-treat 
(mITT)
All subjects who are randomized and have received at least 1 dose 
of study treatment. Subjects will be grouped according to the 
treatment to which they are randomized within the IRT at the start 
of the TP. The mITT population will be the same as the 
Randomized population if all randomized subjects receive at least 
1 dose of study treatment.
Biomarker
All subjects who receive at least 1 dose of study treatment and have 
at least 1 posttreatment biomarker measurement.
Pharmacokinetic
All subjects who receive at least 1 dose of BMS-986165 and have 
any available concentration-time data.
As-treated
All subjects who receive at least 1 dose of double-blind study 
treatment, analyzed according to the treatment actually received, 
regardless of assigned treatment. 
Per Protocol Set (PPS)
All subjects who are compliant with study treatment (compliance 
criteria will be defined in the SAP) and who do not have any 
relevant protocol deviations that may impact the primary efficacy 
endpoint assessments. The PPS will be a supportive efficacy 
analysis population.
9.3
Statistical Analyses
The SAP will be developed and finalized before database lock for the primary efficacy analysis 
and will provide detailed specifications of the analysis of all efficacy endpoints and safety, and it 
will also describe the selection of subjects to be included in the analyses and procedures for 
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accounting for missing data. This section provides a summary of planned statistical analyses of 
the primary and secondary endpoints. 
9.3.1
Efficacy Analysis 
9.3.1.1
Endpoints
Primary Efficacy Endpoint
The primary efficacy endpoint is:
x
Proportion of subjects who meet SRI(4) response at Week 32 (SRI response is defined 
in Section 8.1)
Secondary Efficacy Endpoints
Secondary efficacy endpoints are as follows:
x
Proportion of subjects who meet SRI(4) response at Week 48
x
Proportion of subjects who achieve BICLA response at Week 48, where BICLA 
response is defined as follows:
x
Improvement in all organ systems with activity graded as BILAG-2004 A or B at 
baseline
x
No new organ system with activity graded as BILAG A; no more than 1 new
organ system with activity graded as BILAG B
x
No increase from baseline in SLEDAI-2K (≤0 points for change from baseline 
score)
x
No increase ≥ 10% in the Physician’s Global Assessment of Disease Activity
on a 3-point VAS
x
No discontinuation of IP or use of restricted medications beyond the
protocol allowed threshold before assessment
x
Proportion of subjects who achieve LLDAS at Week 48
x
Proportion of subjects with a CLASI activity score ≥10 at baseline who achieve a 
CLASI response, defined as a decrease of ≥50% from baseline CLASI activity score at 
Week 48
x
Change from baseline in the 40-joint count for tender, swollen, and tender + swollen 
joints at Week 48
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9.3.1.2
Nonresponders
Subjects will be considered nonresponders in the TP for the responder-type efficacy endpoints 
(ie, BICLA and SRI) in the primary and secondary analyses at weeks 32 and 48, respectively, 
if they meet any of the following criteria:
x
Requires CS dose > 7.5 mg/day prednisone or equivalent after Week 20
x
Requires CS rescue therapy beginning after the Week 8 visit 
x
Requires more than 1 burst of CS rescue therapy
x
Requires dose increase in background immunosuppressant or antimalarial medication
x
Requires treatment with medications prohibited by the protocol (Section 6.7.1 and 
APPENDIX 7)
x
Discontinues treatment before the assessment timepoint or has a missing value for the 
particular endpoint
Nonresponder definitions for other time points will be provided in the SAP.
9.3.1.3
Analysis Methodology
General Summaries
Summaries will be provided for the following efficacy variables by each visit for which the 
variable is collected, in addition to the above endpoints:
x
Proportion of subjects who:
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x
Meet SRI(4) response criteria
x
Meet BICLA response criteria
x
Meet LLDAS response criteria
x
Have a CLASI activity score ≥10 at baseline who achieve a CLASI response, 
defined as a decrease of ≥50% from baseline CLASI activity score
x
Are receiving a daily CS dose ≤7.5 mg/day prednisone (or equivalent) in those 
receiving CS at baseline
x
Change from baseline in:
x
BILAG-2004 score
x
SLEDAI-2K score
x
Joint counts for tender, swollen, and tender + swollen joints
x
Physician’s Global Assessment of Disease Activity
x
CLASI activity score in subjects with a CLASI activity score ≥10 at baseline
Statistical Methodology
Efficacy analyses will be performed using the population of randomized subjects.
Endpoint
Statistical Analysis Methods
Primary
The primary endpoint, the proportion of subjects who meet the response 
criteria for SRI(4) at Week 32, will be analyzed using logistic regression 
with covariate for the randomization stratum to compare the response rates 
between each treatment group and placebo. The odds ratio (odds for active 
treatment /odds for placebo) and the corresponding 2-sided 95% confidence 
interval (CI) will be provided from the logistic regression model. 
Additionally, a sensitivity analysis will be conducted using a Cochran-
Mantel-Haenszel (CMH) chi-square test stratified by randomization stratum;
or alternatively a chi-square test if a CMH test cannot be performed. 
Differences in response rates and corresponding 2-sided 95% CI will be 
provided along with the point estimates and corresponding 95% CI for each 
group using a binomial model.
The above analyses will be conducted for the mITT population. The primary 
efficacy analysis will be performed after all subjects have completed 
Week 48 efficacy assessments (or discontinued).
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Endpoint
Statistical Analysis Methods
Secondar
Similar analyses will be performed as for the primary efficacy analyses for 
the proportion-type secondary
 efficacy endpoints to compare 
differences between the active treatment groups and placebo.
The response rates over time will be analyzed using a repeated measure 
model when applicable.
Repeated continuous measures will be analyzed using a mixed effect model 
with treatment, visit, treatment-by-visit interaction, and randomization 
stratum as the fixed effects and changes from baseline within each subject as 
the repeated measurements. The baseline value will be added into the model 
as a covariate. Based on the mixed effect model, the point estimate, and 95% 
CI will be calculated for the difference between each active treatment group 
and the placebo group at each specified visit. 
All analyses will be conducted for the mITT population. The handling of 
missing values will be described in the SAP.
 
Additionally, subgroup analyses to be performed will be described in the SAP.
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9.3.2
Safety Analyses
TSafety analyses will be performed using the As-treated population. The primary safety endpoint is 
a secondary endpoint of the study. For analysis, all recorded AEs will be listed and tabulated by
system organ class, preferred term, and treatment. Vital signs and clinical laboratory test results 
will be listed and summarized by treatment. ECG readings will be evaluated by the investigator 
and abnormalities, if present, will be summarized and listed.
9.3.3
Other Analyses 
9.3.3.1
Pharmacokinetics
PK evaluation is a secondary endpoint. Plasma concentration values will be summarized by dose 
and study day using descriptive statistics. 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 clinical study report.
9.3.3.2
Pharmacodynamics
Pharmacodynamic evaluation is a secondary endpoint. Selected PD endpoints such as IRG 
expression, C3, C4, and anti-dsDNA will be summarized by treatment and timepoint, and their 
corresponding changes and percent change from baseline will be calculated and summarized. 
Change from baseline in lymphocyte count, serum or plasma proteins, genome-wide RNA 
expression, lymphocyte subsets and activation status, etc, will be summarized by time. Baseline 
values will be defined as the last measurement before the first dose.
9.3.4
Interim Analyses 
One interim analysis may be performed after at least 50% of subjects have achieved the Week 32 
primary endpoint to aid in planning for subsequent clinical development. Details and timing of the 
interim analysis will be described in the SAP. Results will be reviewed by an unblinded Sponsor 
team independent from the blinded study team. The unblinded team will provide recommendations 
to the blinded study team as appropriate. The study team responsible for managing the study, 
including medical monitors, will remain blinded. The SAP will further describe any potential 
interim analyses.
9.3.5
Analysis and Reporting
The final database lock will occur once all randomized subjects have completed 48 weeks of 
double-blind treatment (or have discontinued) and the 4-week safety follow-up for those who have
not enrolled into the LTE study IM011074. Details of these efficacy and safety analyses will be 
described in the SAP.
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10
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Dis 2014;73(1):183-90.
22.
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.
23.
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.
24.
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.
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35.
Bretz F, Maurer W, Brannath W, et al. A graphical approach to sequentially rejective 
multiple test procedures. Stat Med 2009;28(4):586-604.
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11
APPENDICES
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APPENDIX 1
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the eCRF is intended to refer to a person 
(Participant) who has consented to participate in the clinical research study.
REGULATORY AND ETHICAL CONSIDERATIONS 
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:
x
Good Clinical Practice (GCP)
x
as defined by the International Council for Harmonisation (ICH)
x
in accordance with the ethical principles underlying European Union Directive 2001/20/EC
x
United States (US) Code of Federal Regulations, Title 21, Part 50 (21CFR50)
x
applicable local requirements
The study will be conducted in compliance with the protocol. The protocol and any amendments
and the participant 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 studywill not usethe services of studypersonnel 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,
participant
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
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applicable, also by local health authority) except where necessary to eliminate an immediate
hazard(s) to study subjects.
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:
x
IRB/IEC 
x
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
participant: (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 sub-investigators 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 participant 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:
x
Provide a copy of the ICF and written information about the study in the language in which 
the participant is most proficient prior to clinical study participation. The language must be 
nontechnical and easily understood.
x
Allow time necessary for participant or participant’s legally acceptable representative to 
inquire about the details of the study.
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x
Obtain an ICF signed and personally dated by the participant or the participant’s legally 
acceptable representative and by the person who conducted the informed consent discussion.
x
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 participant’s legally acceptable representative or legal
guardian, and the participant subsequently becomes capable of making and communicating his or
her informed consent during the study, consent must additionally be obtained from the participant.
Revise the ICF whenever important new information becomes available that is relevant to the
participant’s consent. The investigator, or a person designated by the investigator, should fully
inform the participant or the participant’s legally acceptable representative or legal guardian, of all
pertinent aspects of the study and of any new information relevant to the participant’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 participants’ signed ICF and,
in the US, the participants’ signed Health Insurance Portability and Accountability Act (HIPAA)
Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct
access to participant records.
Subjects unable to give their written consent (eg, those with stroke or severe dementia) may
only be enrolled in the studywith the consent of a legally acceptable representative. The participant
must also be informed about the nature of the study to the extent compatible with his or her
understanding, and should this participant become capable, he or she should personally sign and
date the consent form as soon as possible. The explicit wish of a participant 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 participants 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,
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/healthrecords (EMRs/EHRs),
adverse event tracking/reporting, protocol-required assessments, and/or drug accountability
records).
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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:
x
amount received and placed in storage area
x
amount currently in storage area
x
label identification number or batch number
x
amount dispensed to and returned by each participant, including 
unique participant identifiers
x
amount transferred to another area/site for dispensing or storage
x
nonstudy disposition (eg, lost, wasted)
x
amount destroyed at study site, if applicable
x
amount returned to BMS
x
retain samples for bioavailability/bioequivalence, if applicable
x
dates and initials of person responsible for Investigational Product 
dispensing/accountability, as per the Delegation of Authority Form.
Sourced by site, and 
not supplied by BMS 
or its vendors 
(examples include 
investigational 
product sourced from 
the site 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 standard operating 
procedures of the sourcing pharmacy.
These records should include:
x
label identification number or batch number
x
amount dispensed to and returned by each participant, including 
unique participant identifiers
x
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.
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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 adverse events (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 (EDC) tool, electronic CRFs will 
be prepared for all data collection fields except for fields specific to serious adverse events 
(SAEs) and pregnancy, which will be reported on the electronic SAE form and Pregnancy 
Surveillance form, respectively. If an electronic SAE form is not available, a paper SAE form 
can be used. Spaces may be left blank only in those circumstances permitted by study-specific 
CRF completion guidelines provided by Sponsor or designee.
The confidentiality of records that could identify participants 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.
The completed CRF and SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated 
by the investigator or qualified physician who is a sub-investigator and who is delegated this task 
on the Delegation of Authority Form. Sub-investigators in Japan may not be delegated the CRF 
approval task. For electronic CRFs, review and approval/signature is completed electronically 
through the BMS EDC 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 BMS EDC 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.
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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 (as 
applicable; some sites will return unused study treatments depending on circumstances).
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) (eg, study 
treatments sourced from the 
site’s 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:
x
On-site disposal practices must not expose humans to risks from the drug.
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x
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
x
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.
x
Records are maintained that allow for traceability of each container, including the date 
disposed, quantity disposed, and identification of the person disposing the containers. The 
method of disposal (eg, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor) must be documented.
x
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.
For sites that will not destroy study treatment on-site, it is the investigator’s or designee’s 
responsibility to arrange for disposal of all empty study treatment containers, 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 return of full or partially used study treatments supplied by BMS or its vendors will be 
arranged by the responsible Study Monitor.
CLINICAL STUDY REPORT AND PUBLICATIONS
A signatory investigator must be selected to sign the clinical study report.
For this protocol, the signatory investigator will be selected as appropriate based on one or more 
of the following criteria:
x
External principal investigator designated at protocol development
x
National Coordinating investigator
x
Study Steering Committee chair or their designee
x
Participant recruitment (eg, among the top quartile of enrollers)
x
Involvement in trial design
x
Regional representation (eg, among top quartile of enrollers from a specified region or country)
x
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 2
ABBREVIATIONS AND TRADEMARKS
Term
Definition
6-MP
6-mercaptopurine
ACR
American College of Rheumatology
ADL
activity of daily living
AE
adverse event
AEI
adverse event of interest
ALT
alanine aminotransferase
ANA
antinuclear antibody
anti-Sm
anti-Smith
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC(0-24)
area under the concentration-time curve from 0 to 24 hours
AUC(INF)
area under the concentration-time curve extrapolated to infinity
AUC(TAU)
area under the concentration-time curve in one dosing interval
AZA
azathioprine
β-HCG
beta-human chorionic gonadotropin
BCRP
breast cancer resistance protein
BICLA
BILAG-based Composite Lupus Assessment
BID
bis in die (twice daily)
BILAG
British Isles Lupus Assessment Group
BMS
Bristol-Myers Squibb
Cavg
average concentration during a dosing interval
CFR
Code of Federal Regulations
CI
confidence interval
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
Cmax
maximum plasma concentration
CMH
Cochran-Mantel-Haenszel
CRF
case report form
CRS
Central Review Services
CS
corticosteroid(s)
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Term
Definition
CTA
clinical trial agreement
Ctrough
trough observed plasma concentration
CYP450
cytochrome p-450
DDI
drug-drug interaction
DILI
drug-induced liver injury
DMC
data monitoring committee
dsDNA
double-stranded deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
Emax
direct effect
FIH
first-in-human
FP
follow-up period
GCP
Good Clinical Practice
HBc
hepatitis B core
HBs
hepatitis B surface
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
hsCRP
high-sensitivity C-reactive protein
IB
Investigator Brochure
IBD
inflammatory bowel disease
IC50
half-maximal inhibitory concentration
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IFN
interferon
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Term
Definition
Ig
immunoglobulin
IGRA
interferon gamma release assay
IL
interleukin
IMP
investigational medicinal product
INR
international normalized ratio
IP
investigational product
IRB
Institutional Review Board
IRG
interferon-regulated gene
IRT
interactive response technology
IV
intravenous
JAK
Janus kinase
KLH
keyhole limpet hemocyanin
LLDAS
Lupus Low Disease Activity State
LTE
long-term extension
mITT
modified intent-to-treat
MMF
mycophenolate mofetil/mycophenolic acid
MTX
methotrexate
NOAEL
no observed adverse effect level
NSAID
nonsteroidal anti-inflammatory drug
NYHA
New York Heart Association
OTC
over-the-counter
PD
pharmacodynamic(s)
PE
physical examination
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PPS
Per Protocol Set
QD
quaque die (once daily)
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Term
Definition
RBC
red blood cell
RNA
ribonucleic acid
RNP
ribonuclear protein
SAE
serious adverse event
SAP
statistical analysis plan
SLE
systemic lupus erythematosus
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SLICC
Systemic Lupus International Collaborating Clinics
SP
screening period
SRI
Systemic Lupus Erythematosus Responder Index
STAT
signal transducer and activator of transcription
T4
thyroxine
TB
tuberculosis
TBNK
T cell, B cell, natural killer cell
TDAR
T cell-dependent antibody response
Tmax
time to maximum plasma concentration 
TP
treatment period
TSH
thyroid-stimulating hormone
TYK2
tyrosine kinase 2
UK
United Kingdom
ULN
upper limit of normal
UPCR
urine protein/creatinine ratio
US/USA
United States of America
VAS
visual analog scale
WOCBP
women of childbearing potential
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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
x
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, 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.
x
Exacerbation of a chronic or intermittent preexisting condition including either an increase 
in frequency and/or intensity of the condition.
x
New conditions detected or diagnosed after study intervention administration even though 
it may have been present before the start of the study.
x
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
x
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
x
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
x
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
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.
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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: 
x
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)
x
elective surgery, planned prior to signing consent
x
admissions as per protocol for a planned medical/surgical procedure
x
routine health assessment requiring admission for baseline/trending of health status (eg, 
routine colonoscopy)
x
medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases
x
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)
x
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 8.3.8 for the definition of potential DILI). 
Pregnancy and potential DILI must follow the same transmission timing and processes to BMS as 
used for SAEs (see Section 8.3.6 for reporting pregnancies).
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EVALUATING AES AND SAES
Assessment of Intensity
The intensity of AEs is determined by a physician and will use the following levels:
x
Mild: An event that is easily tolerated by the subject, causing minimal discomfort, and not 
interfering with everyday activities.
x
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.
x
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
x
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.
x
The investigator will use clinical judgment to determine the relationship.
x
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.
x
The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.
x
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.
x
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.
x
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.
x
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 
 
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: 
SAE Fax Number: 
Americas: 
Europe/East Asia-Pacific:
SAE Telephone Contact - For questions on SAE/pregnancy reporting, please call:
Americas: 
Europe/East Asia-Pacific: 
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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:
x
Premenarchal
x
Premenopausal female with 1 of the following:
o
Documented hysterectomy
o
Documented bilateral salpingectomy
o
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.
x
Postmenopausal female 
o
A postmenopausal state is defined as 12 months of amenorrhea in a woman older than 
45 years in the absence of other biological or physiological causes. In addition, women 
younger than 55 years must have a serum follicle-stimulating hormone (FSH) level 
> 40 mIU/mL to confirm menopause.
Note: Women 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.
x
1 week minimum for vaginal hormonal products (rings, creams, gels)
x
4 week minimum for transdermal products
x
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 CHILDBEARING 
POTENTIAL
One of the highly effective methods 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
x
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation
o
oral 
o
intravaginal 
o
transdermal 
x
Combined (estrogen- and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy
x
Progestogen-only hormonal contraception associated with inhibition of ovulation
o
oral 
o
injectable
x
Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy
Highly Effective Methods That Are User-Independent 
x
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationb
x
Intrauterine deviceb
x
Intrauterine hormone-releasing systemb
x
Bilateral tubal occlusion
x
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. 
x
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 participant.
x
It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
x
WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 1.3.
x
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants 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 participants participating in clinical 
studies.  
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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.
Less Than Highly Effective Contraceptive Methods That Are User-Dependent 
Failure rate of > 1% per year when used consistently and correctly.
x
Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously
x
Diaphragm with spermicide
x
Cervical cap with spermicide
x
Vaginal sponge with spermicide
x
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action
Unacceptable Methods of Contraception
x
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
x
Withdrawal (coitus interruptus).
x
Spermicide only
x
Lactation amenorrhea method
CONTRACEPTION GUIDANCE FOR MALE SUBJECTS WITH FEMALE 
PARTNER(S) OF CHILDBEARING POTENTIAL 
Male subjects with female partners of childbearing potential are eligible to participate if they agree 
to the following during the treatment:
x
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.
x
Condom use is not required.
x
Female partners of men participating in the study to consider use of effective methods of 
contraception until the end of relevant systemic exposure, defined as the duration of the study 
treatment.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 8.3.6.
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APPENDIX 5
SYSTEMIC LUPUS INTERNATIONAL COLLABORATING
CLINICS CLASSIFICATION CRITERIA FOR SYSTEMIC LUPUS
ERYTHEMATOSUS
*Notes:
CLINICAL CRITERIA
1) Acute Cutaneous Lupus OR Subacute Cutaneous Lupus
o
Acute cutaneous lupus: lupus malar rash (do not count if malar discoid), bullous lupus,
toxic epidermal necrolysis variant of SLE, maculopapular lupus rash, photosensitive lupus
rash (in the absence of dermatomyositis)
o
Subacute cutaneous lupus: nonindurated psoriaform and/or annular polycyclic lesions that
resolve without scarring, although occasionally with postinflammatory dyspigmentation or
telangiectasias)
2) Chronic Cutaneous Lupus
Classic discoid rash localized (above the neck) or generalized (above and below the neck),
hypertrophic (verrucous) lupus, lupus panniculitis (profundus), mucosal lupus, lupus
erythematosus tumidus, chilblains lupus, discoid lupus/lichen planus overlap
3) Oral Ulcers OR Nasal Ulcers
o
Oral: palate, buccal, tongue
o
Nasal ulcers
o
In the absence of other causes, such as vasculitis, Behҫet’s disease, infection (herpes virus),
inflammatory bowel disease, reactive arthritis, and acidic foods
4) Nonscarring Alopecia
Diffuse thinning or hair fragility with visible broken hairs, in the absence of other causes such 
as alopecia areata, drugs, iron deficiency, and androgenic alopecia
5) Synovitis Involving 2 Or More Joints
x
Characterized by swelling or effusion
x
OR tenderness in 2 or more joints and at least 30 minutes of morning stiffness
6) Serositis
x
Typical pleurisy for more than 1 day OR pleural effusions OR pleural rub
x
Typical pericardial pain (pain with recumbency improved by sitting forward) for more 
than 1 day OR pericardial effusion OR pericardial rub OR pericarditis by 
electrocardiography
x
In the absence of other causes, such as infection, uremia, and Dressler’s pericarditis
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7) Renal
Urine protein–to-creatinine ratio (or 24-hour urine protein) representing 500 mg protein per 
24 hours OR red blood cell casts
8) Neurologic
Seizures, psychosis, mononeuritis multiplex (in the absence of other known causes such as 
primary vasculitis), myelitis, peripheral or cranial neuropathy (in the absence of other known 
causes such as primary vasculitis, infection, and diabetes mellitus), acute confusional state (in 
the absence of other causes, including toxic/metabolic, uremia, drugs)
9) Hemolytic Anemia
10) Leukopenia (< 4000/mm3) OR Lymphopenia (< 1000/mm3)
Leukopenia at least once: In the absence of other known causes such as Felty’s syndrome, drugs, 
and portal hypertension.
Lymphopenia at least once: in the absence of other known causes such as corticosteroids, drugs, 
and infection
11) Thrombocytopenia (< 100,000/mm3)
At least once in the absence of other known causes such as drugs, portal hypertension, and 
thrombotic thrombocytopenic purpura
IMMUNOLOGIC CRITERIA
1) ANA level above laboratory reference range
2) Anti-dsDNA antibody level above laboratory reference range (or 2-fold the reference range if 
tested by enzyme-linked immunosorbent assay [ELISA]); indeterminate results are considered 
positive
3) Anti-Sm: presence of antibody to Sm nuclear antigen
4) Antiphospholipid antibody positivity, as determined by
x
Positive test for lupus anticoagulant
x
False-positive test result for rapid plasma reagin (RPR)
x
Medium- or high-titer anticardiolipin antibody level (IgA, IgG, or IgM)
x
Positive test result for anti–2-glycoprotein I (IgA, IgG, or IgM)
5) Low complement (C3, C4, or CH50)
6) Direct Coombs test (in the absence of hemolytic anemia)
Source:
Petri M, Orbai AM, Alarcon GS, et al. Derivation of the Systemic Lupus International 
Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 
2012 Aug;64(8):2677-86.
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APPENDIX 6
COMMONLY USED CORTICOSTEROID EQUIVALENTS
Medication
Dose Equivalence
Prednisone
20 mg
Cortisone
100 mg
Hydrocortisone
80 mg
Prednisolone
20 mg
Methylprednisolone
16 mg
Triamcinolone
16 mg
Budesonide
4 mg
Dexamethasone
3 mg
Betamethasone
2.4 mg
Deflazacort
26 mg
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APPENDIX 7
REQUIRED RECOVERY (WASHOUT) TIMES FOR SPECIFIC 
MEDICATIONS PRIOR TO SCREENING
Medications
Discontinuation Prior to Signing 
Consent
Abatacept (CTLA4Ig)
12 weeks
Acthar® gel (repository corticotropin injection)
6 weeks
Adalimumab
12 weeks
Alefacept
8 weeks
AMG 623
12 weeks
Anakinra
12 weeks
Apremilast
4 weeks
Atacicept (TACI-Ig)
48 weeks
Belimumab
24 weeks
BIIB059
15 weeks
Certolizumab pegol
24 weeks
Cyclophosphamide
24 weeks
Cyclosporine
4 weeks for systemic use (oral, IV, etc)
Danazol
4 weeks
Dapsone
4 weeks
Eculizumab
12 weeks
Efalizumab
8 weeks
Epratuzumab
18 weeks
Etanercept
4 weeks
Infliximab
12 weeks
Intravenous globulin
4 weeks
Leflunomide
36 weeks
Lenalidomide with cholestyramine
24 weeks
Lulizumab
6 weeks
Lupuzor (IPP-201101)
12 weeks
Memantine
4 weeks
Natalizumab
12 weeks
Obinutuzumab
26 weeks
Ocrelizumab
24 weeks
Ofatumumab
26 weeks
Plasmapheresis
24 weeks
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Medications
Discontinuation Prior to Signing 
Consent
Retinoids (oral isotretinoin, and acitretin; topical 
retinoids are allowed)
4 weeks
Rituximab
24 weeks
Sifalimumab
26 weeks
Sirolimus
4 weeks
Sulfasalazine
4 weeks
Tabalumab
14 weeks
Tacrolimus
4 weeks for systemic use (oral, IV, etc)
Thalidomide
4 weeks
Tocilizumab
12 weeks
Tofacitinib
4 weeks
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APPENDIX 8
DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL 
DISORDERS IV
Alcohol abuse:
In the past year, have you:
x
Found that drinking – or being sick from drinking – often interfered with taking care of your 
home or family? Or caused job troubles? Or school problems?
x
More than once gotten into situations while or after drinking that increased your chances of
getting hurt (such as driving, swimming, using machinery, walking in a dangerous area, or 
having unsafe sex)?
x
More than once gotten arrested, been held at a police station, or had other legal problems 
because of your drinking?
x
Continued to drink even though it was causing trouble with your family or friends? 
The presence of any 1 of the above is considered indicative of alcohol abuse.
Alcohol dependence:
In the past year, have you:
x
Had to drink much more than you once did to get the effect you want? Or found that your usual 
number of drinks had much less effect than before?
x
Found that when the effects of alcohol were wearing off, you had withdrawal symptoms, such 
as trouble sleeping, shakiness, restlessness, nausea, sweating, a racing heart, or a seizure? Or 
sensed things that were not there?
x
Had times when you ended up drinking more, or longer, than you intended?
x
More than once wanted to cut down or stop drinking, or tried to, but couldn’t?
x
Spent a lot of time drinking? Or being sick or getting over other aftereffects?
x
Given up or cut back on activities that were important or interesting to you, or gave you 
pleasure, in order to drink?
x
Continued to drink even though it was making you feel depressed or anxious or adding to 
another health problem? Or after having had a memory blackout?
The presence of any 3 of the above is considered indicative of alcohol dependence.
National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. Alcohol use 
disorder: a comparison between DSM-IV and DSM-5. NIH Publication No. 13-7999. Reviewed 
July 2016.
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APPENDIX 9
INTERPRETATION OF HEPATITIS B SEROLOGIC TEST 
RESULTS
Because BMS-986165 is expected to demonstrate immunosuppressive effects, it is imperative to 
carefully evaluate and exclude participants with potentially active hepatitis B infection. For this 
reason, to fully evaluate a participant’s eligibility for enrollment, the exclusion criterion (see 
Section 5.2) requires interpretation of data from 3 standard tests for hepatitis B, ie, measurement 
of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B 
surface antibody (anti-HBs).
The participant’s eligibility for enrollment should be assessed as described below:
x
Hepatitis B serological test negative (neg) for all results may be included in the study
x
HBsAg (neg), anti-HBc (neg), and anti-HBs positive (POS) may be included in the study 
(immunized due to hepatitis B vaccination)
x
HBsAg (neg), anti-HBc (POS), and anti-HBs (POS) are to be excluded from the study (immune 
due to natural infection exposure)
x
Participants that are HBsAg (POS) are excluded from the study (acute or chronic infection)
x
Participants that are anti-HBc (POS) are excluded from the study (acute or chronic infection)
x
Participants that are HBsAg (neg), anti-HBc (POS), and anti-HBs (neg) are to be excluded 
from the study (interpretation unclear)
Please refer to the schematic “Interpretation of Hepatitis B Serologic Test Results” (below) 
provided by the Department of Health and Human Services, Centers for Disease Control and 
Prevention.
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APPENDIX 10
BRITISH ISLES LUPUS ASSESSMENT GROUP INDEX – 2004
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Sources:
Isenberg, DA, Rahman A, Allen E, et al. BILAG 2004. Development and initial validation of an 
updated version of the British Isles Lupus Assessment Group’s disease activity index for patients 
with systemic lupus erythematosus. Rheumatology (Oxford) 2005;44(7):902-6.
Yee CS, Farewell V, Isenberg DA, et al. Revised British Isles Lupus Assessment Group 2004 
Index - A Reliable Tool for Assessment of Systemic Lupus Erythematosus Activity. Arthritis 
Rheum 2006;54:3300–05.
Yee CS, Farewell V, Isenberg DA, et al. British Isles Lupus Assessment Group 2004 index is valid 
for assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 
2007;56(12):4113-19.
Yee CS, Cresswell L, Farewell V, et al: Numerical scoring for the BILAG-2004 index. 
Rheumatology (Oxford) 2010 Sep;49(9):1665-9.
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APPENDIX 11
SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY 
INDEX 2000 DISEASE ACTIVITY QUESTIONNAIRE
Note: Detailed definitions of the individual items are included in a quick reference guide for sites.
For an item to be scored the indicated weight, the manifestation must have been present in the past 
30 days.
The glossary of the terms is adjacent on the form itself.
Enter weight in SLEDAI-2K Score column if descriptor is present at the time of the visit or in the 
preceding 30 days.
Sources:
Gladman, DD., Ibañez, D., Urowitz, MB. Systemic Lupus Erythematosus Disease Activity Index 
2000. J Rheumatol 2002;29:288-91.
Touma Z, Urowitz MB, Gladman DD. SLEDAI-2K for a 30-day window. Lupus 2010;19:49-51.
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APPENDIX 12
CUTANEOUS LUPUS ERYTHEMATOSUS DISEASE AREA AND 
SEVERITY INDEX (CLASI)
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Sources:
Albrecht J, Taylor L, Berlin JA, et al. The CLASI (Cutaneous Lupus Erythematosus Disease Area 
and Severity Index): An outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol 
2005;125:889 -94.
Bonilla-Martinez ZL, Albrecht J, Troxel AB, et al. The Cutaneous Lupus Erythematosus Disease 
Area and Severity Index - A responsive instrument to measure activity and damage in patients with 
cutaneous lupus erythematosus. Arch Dermatol 2008;144(2):173-80.
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15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
127
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Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
128
APPENDIX 17
OTHER ASSESSMENTS
Physician’s Global Assessment of Disease Activity
How do you assess your patient’s (the subject’s) current disease activity as compared to the last
visit? Please mark the line below.
Patient’s Global Assessment of Disease Activity
Considering all the ways in which your lupus has affected you in the PAST WEEK, please make
a mark on the line below to show how you are doing.
Very Poorly
Very Well
Patient-Reported Pain Assessment
On a scale of 0 to 10, with 0 being no pain at all and 10 being the worst pain imaginable, how
would you rate your pain in the PAST WEEK?
Please circle the number below that represents your pain.
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Clinical Protocol
IM011021
BMS-986165
TYK2 Inhibitor
15-Apr-2020; Revised Protocol 04, Final Approved
BMS Confidential
129
APPENDIX 18
MORPHINE MILLIGRAM EQUIVALENTS FOR OPIOIDS
The following table shows daily morphine milligram equivalents for some opioids. This list is not 
exhaustive, and the 30 mg morphine equivalence limit applies to all opioid analgesics even if they 
are not listed here.
Opioid
30 mg morphine equivalent
butorphanol
4.3 mg/day
codeine
200 mg/day
dihydrocodeine
120 mg/day
fentanyl transdermal
12.5 mcg/hr
hydrocodone
30 mg/day
hydromorphone
7.5 mg/day
levorphanol tartrate
2.7 mg/day
meperidine HCl
300 mg/day
oxycodone
20 mg/day
oxymorphone
10 mg/day
pentazocine
81.1 mg/day
tapentadol
75 mg/day
tramadol
300 mg/day
Reference: 
Centers for Medicare and Medicaid Services. Opioid Oral Morphine Milligram Equivalent 
Conversion Factors. 
https://www.cms.gov/Medicare/Prescription-Drug-
Coverage/PrescriptionDrugCovContra/Downloads/Opioid-Morphine-EQ-Conversion-Factors-
Aug-2017.pdf. Accessed 04-Jun-2019.
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SAP_001.pdf: 
Official Title of Study: 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and 
Safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus 
 
NCT Number: NCT03252587 
Document Date (Date in which document was last revised): Dec 20, 2021 


Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 1 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
Statistical Analysis Plan 
Sponsor: 
Bristol-Myers Squibb 
Protocol No: 
IM011021 
Protocol Date: 
15-April-2020
Protocol Version 
No.: 
Revised Protocol v4.0 
Title: 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate Efficacy and Safety of BMS-986165 in Subjects with Systemic 
Lupus Erythematosus 
SAP Version No. 
4.0 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 2 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
Table of Contents 
Table of Contents 
ts...................................................................................................................................... 2 
1.0 Purpose 
e............................................................................................................................. ................. 6 
2.0 Scope 
e .................................................................................................................................................. 6 
3.0 Introduction 
n ............................................................................................................................. ........... 6 
4.0 Study Objectives s ................................................................................................................................. 6 
4.1 Primary Efficacy ................................................................................................................. 6 
4.2 Secondary Efficacy ............................................................................................................ 6 
4.3 Safety ................................................................................................................................. 6 
4.4 Pharmacokinetics ............................................................................................................... 6 
4.5 Pharmacodynamics ........................................................................................................... 6 
5.0 Study Desig  
n............................................................................................................................. ......... 7 
5.1 Sample Size Considerations .............................................................................................. 8 
5.2 Randomization ................................................................................................................... 8 
5.3 Unblinding Information ....................................................................................................... 8 
5.4 Summary of Changes to Version 2.0 of SAP ..................................................................... 9 
5.4.1 Changes due to protocol amendments after finalization of SAP V1.0 ........................ 9 
5.4.2 Additional Changes to SAP V2.0 ................................................................................ 9 
5.5 Summary of Changes to Version 3.0 of SAP ................................................................... 10 
5.6 Summary of Changes to Version 4.0 of SAP ................................................................... 11 
6.0 Study Variables ............................................................................................................................... 11 
6.1 Efficacy Assessments ...................................................................................................... 11 
6.2 Composite Measures ....................................................................................................... 13 
6.4 Safety ............................................................................................................................... 16 
6.5 Predetermined Covariates and Prognostic Factors ......................................................... 16 
7.0 Definitions ....................................................................................................................................... 17 
7.1 General ............................................................................................................................ 17 
7.2 Analysis Visits Windows .................................................................................................. 18 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
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8.0 Populations for Analyses................................................................................................................. 18 
8.1 Enrolled ............................................................................................................................ 18 
8.2 Randomized ..................................................................................................................... 18 
8.3 All-treated ......................................................................................................................... 19 
8.4 Biomarker ......................................................................................................................... 19 
8.5 Pharmacokinetic .............................................................................................................. 19 
9.0 Analysis and Reporting ................................................................................................................... 19 
10.0 Data Review .................................................................................................................................. 19 
10.1 Data Handling and Transfer ........................................................................................... 19 
11.0 Statistical Methods ........................................................................................................................ 19 
11.1 Subject Disposition ........................................................................................................ 20 
11.2 Demographic and Baseline Characteristics ................................................................... 20 
11.3 Relevant Protocol Deviations ......................................................................................... 21 
11.4 Exposure ........................................................................................................................ 21 
11.4.1 Duration of Exposure.............................................................................................. 21 
11.4.2 Summary of Dosing ................................................................................................ 21 
11.4.3 Compliance ............................................................................................................ 21 
11.5 Prior and Concomitant Medications ............................................................................... 22 
11.5.1 Prior Corticosteroid Use ......................................................................................... 22 
11.5.2 Concomitant Corticosteroid Use ............................................................................. 22 
11.6 Medical History .............................................................................................................. 23 
11.7 Efficacy Analyses ........................................................................................................... 23 
11.7.1 Primary Endpoint .................................................................................................... 24 
11.7.2 Secondary Endpoints ............................................................................................. 26 
11.7.2.1 SRI(4) Response at Week 48 ........................................................................... 26 
11.7.2.2 BICLA Response at Week 48 ........................................................................... 27 
11.7.2.3 CLASI-A Response (CLASI-50) at Week 48 ..................................................... 28 
11.7.2.4 LLDAS Response at Week 48 .......................................................................... 28 
11.7.2.5 Tender and Swollen Joint Count at Week 48 .................................................... 29 
11.7.4 Subgroup Analysis ................................................................................................. 31 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
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.  All rights reserved. 
11.8 Safety Analyses ............................................................................................................. 36 
11.8.1 Adverse Events ...................................................................................................... 37 
11.8.2 Adverse Events of Interest ..................................................................................... 38 
11.8.3 Deaths and Serious Adverse Events ...................................................................... 38 
11.8.4 Laboratory Data...................................................................................................... 38 
11.8.5 Vital Signs .............................................................................................................. 39 
11.8.6 ECG ....................................................................................................................... 39 
11.8.7 Physical Examination ............................................................................................. 40 
11.9 Statistical impacts due to Covid-19 ................................................................................ 40 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 6 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
1.0 Purpose 
The statistical analysis plan (SAP) describes the statistical methods to be used during the reporting 
and analyses of data collected under Bristol-Myers Squibb IM011021 revised protocol version 4.0 
dated 15 April 2020. 
2.0 Scope 
This plan is a document that will be created during the trial start-up and finalized prior to study 
unblinding. The SAP will be maintained throughout the lifecycle of the trial.  If the SAP needs to be 
updated after finalization, then each version of the SAP will require sign off from the Biostatistics Asset 
Lead (BAL) or the BMS GBDS Lead. 
The SAP outlines the following: 
x 
Study objectives 
x 
Study design 
x 
Variables analyzed and analysis sets 
x 
Applicable study definitions 
x 
Statistical methods regarding relevant protocol deviations, study drug exposure, efficacy 
analysis, concomitant medications, adverse events handling, laboratory data and physical 
examinations 
x 
Statistical methods for handling missing data and multiplicity 
3.0 Introduction 
The SAP describes the statistical methods to be used during the reporting and analyses of data 
collected under Bristol-Myers Squibb Protocol IM011021 version 4.0 (dated 15-Apr-2020). The SAP 
should be read in conjunction with the study protocol and case report form (CRF). This version of the 
plan has been developed using the protocol dated 15Apr2020 and CRF dated 14Jan2021.  
4.0 Study Objectives 
4.1 Primary Efficacy 
x 
To assess the effect of BMS-986165 on Systemic Lupus Erythematosus (SLE) Responder 
Index (4) (SRI[4]) at Week 32 in subjects with SLE  
4.2 Secondary Efficacy 
x 
To assess the effect of BMS-986165 on measures of global and organ-specific SLE clinical 
response 
4.3 Safety 
x 
To assess the safety and tolerability of BMS-986165 in subjects with SLE 
4.4 Pharmacokinetics 
x 
To assess PK of BMS-986165 and its active metabolite (BMT-153261) in subjects with SLE 
4.5 Pharmacodynamics 
x 
To assess the effect of BMS-986165 on PD markers in subjects with SLE 
 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 7 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
5.0 Study Design 
This is a randomized, placebo-controlled, double-blind, multicenter study to evaluate the efficacy and 
safety of BMS-986165 in subjects with SLE. Following a screening period of up to 4 weeks, 
approximately 360 subjects are to be randomized (1:1:1:1) via interactive response technology (IRT) to 
1 of 4 treatments: 
  
x 
BMS-986165 12 mg once daily (QD) 
x 
BMS-986165 6 mg twice daily (BID) 
x 
BMS-986165 3 mg BID 
x 
placebo  
 
Randomization is planned to be stratified by incoming corticosteroid (CS) dose, SLE Disease Activity 
Index 2000 (SLEDAI-2K) score and region (see section 5.2 for details). The total duration of study 
participation for each subject is up to approximately 56 weeks (392 days), including up to a 4-week (28-
day) screening period (SP), a 48-week (336-day) treatment period (TP), and a 4-week (28-day) follow-
up period (FP) for subjects who do not continue into the long term extension (LTE) study (IM011074). 
The primary efficacy analysis will be based on Week 32 efficacy assessments. The study design is 
summarized in Figure 1. 
 
Enrolled subjects will have received background therapy for at least 12 weeks including at a stable dose 
for at least 8 weeks before the screening visit, throughout the screening period and remain stable 
throughout the study. If on CS, the dose must be stable for at least 2 weeks before the screening visit, 
and throughout the screening period. A dose up to 30 mg/day prednisone or equivalent (as described 
in protocol Appendix 6) is permitted at the screening visit. Tapering of CS may begin at any time after 
the first dose on Day 1 and must start by Week 8. By Week 20 all subjects must have a CS dose of İ 
7.5 mg prednisone or equivalent (if this is not possible, the subject is to remain on treatment, but will be 
a non-responder for analysis purposes). The CS dose must remain stable from Week 20 until Week 32 
and tapering may resume at Week 32. The last day for CS taper is the Week 40 visit, and the CS dose 
must remain stable from Week 40 until Week 48. 
 
 
Details of physical examination, vital sign measurement, 12-lead ECG, and clinical laboratory 
evaluations are to be collected at all or at selected visits during the treatment and follow up period. 
Blood samples for PK and PD analysis are also to be collected for all subjects. 
 
 
 
A listing of measurements to be collected by visit are detailed in the schedule of events in Appendix 2. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 9 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
staff) after the week 48 database lock. However, if there is a medical emergency or pregnancy where 
knowledge of investigational product (IP) is critical to the subject’s management the blind may be broken 
by the Investigator. 
The Data Monitoring Committee (DMC) provides oversight of safety consideration throughout the study. 
A separate unblinded team, comprised of an unblinded Independent Reporting Statistician (IRS) and 
unblinded programmer(s), will produce output for the DMC using masked treatments. Treatment 
decodes may only be requested by DMC Chair and will be provided by the IRS. Data summaries and 
listings will be transmitted via a secure portal by IRS to only the DMC members. Additional details 
regarding the DMC process and unblinding are provided in the DMC charter. 
Designated staff of BMS may be unblinded prior to database lock to facilitate the bioanalytical analysis 
of PK and biomarker samples and immunogenicity. 
 
 
 
  
5.4 Summary of Changes to Version 2.0 of SAP  
No analyses were performed prior to the revision of this SAP.  
5.4.1 Changes due to protocol amendments after finalization of SAP V1.0 
 
2. Revised the testing strategy to be used for the primary and secondary endpoints (Section 
9.3.1.4 of protocol) 
3. Week 48 endpoints moved into the multiplicity-controlled hierarchy for better alignment with 
regulatory guidance documents 
4. Non-responder imputation (NRI) section updated: updated to clarify that this NRI is applicable 
to the primary and secondary endpoints at Week 32 and Week 48. 
5. Single randomization stratum combining Region (North America, Latin America, Rest of 
World, Japan [other stratification factors will not EH DSSOLHG LQ -DSDQ@ &6 GRVH DW EDVHOLQH 
10 mg/day or < 10 mg/day) and SLEDAI-. DW EDVHOLQH   RU   DGGHG IRU logistic 
regression, Cochran-Mantel-Haenszel and repeated measures analysis: Clarification of how 
to handle the lack of CS and SLEDAI-2K stratification within Japanese subjects 
6. Revised the testing hierarchy for the QD and BID branches: Testing strategy revised to align 
with revision of the Week 48 endpoints to secondary endpoints 
. The 
revised testing strategy ensures the familywise Type I error is protected for the primary and 
secondary endpoints. 
7. The planned 32-week database lock has been removed: Since the key secondary endpoints 
will now be assessed at Week 48 no database lock will occur until all randomized subjects 
have completed 48 weeks of double-blind treatment (or have discontinued) 
 
5.4.2 Additional Changes to SAP V2.0  
 
1. Changes to the description of the composite endpoints for efficacy (aligned with source 
literature): 
a. SRI response: 
i. correction: no new BILAG A (severe disease activity) and (instead of “or” as 
indicated in the protocol) not more than 1 new BILAG B (moderate disease 
activity) organ domain grade since baseline 
ii. clarification: “new BILAG grade” should be interpreted as “worsened BILAG 
grade compared to baseline” 
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 10 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
iii. correction: response only if PGA change from baseline <0.3 (instead of 
“<=0.3” as implied in the protocol description) (see Furie et al. Arthritis 
Rheum. 2009 61(9): 1143–1151; and 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 Science & Medicine 2014;1: e000031. 
doi:10.1136/lupus2014-000031) 
b. BICLA response: “new BILAG grade” should interpreted as “worsened BILAG 
grade compared to baseline” 
c. LLDAS response: “new BILAG grade” should interpreted as “worsened BILAG 
grade compared to previous assessment” 
2. Added for clarification to the CTP: All hypothesis test will be based on Wald tests for odds 
ratio estimates for comparisons of the treatment groups and the placebo group obtained from 
the logistic regression models 
4. Removal of per protocol analyses 
5. Removal of all LOCF analyses 
6. Modified sensitivity analyses, including addition of a treatment policy approach  
7. Added a tipping point analysis for the primary endpoint   
9. Various changes to format and structure to improve clarity 
11. Refinement of NRI imputation method including the list of prohibited medications 
12. Updated PK and Biomarker analyses  
5.5 Summary of Changes to Version 3.0 of SAP  
No analyses were performed prior to the revision of this SAP. 
1. Added clarification for the first dose date in section 7.1 
2. Added one additional condition in sections 11.7.1 and 11.7.2.2:  
a. Subjects takes any medications included in protocol Appendix 7 between first dose 
date and efficacy assessment visit 
3. Deleted one condition in sections 11.7.1 and 11.7.2.2:  
a. Initiations and/or increases which occur for less than 4 days are permitted 
4. Deleted the bar chart in sections 11.7.1, 11.7.2.3 and 11.7.2.4 
5. In section 11.7.1, in case the logistic regression model fit is not stable the region stratification 
factor may be removed from the model. The stratification factors were updated to: CS dose ҆ 
10 mg/day Yes or No, SLEDAI-2K score ҆ 10 Yes or No, and Japan. 
6. Added clarification for analysis time points in section 11.7.2.5 
7. Changed “interferon regulated genes” to “interferon” in section 11.7.4 
8. Added “at baseline” for subgroup analyses referring to CS Use, anti-malarial use, and 
immunosuppressant use in section 11.7.4 
10. Added clarification for analysis time points in section 11.7.5 
11. Deleted the following condition in section 11.8.4: 
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a. 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. 
12. Modified the QTcF calculation in section 11.8.6 
13. Updated the pharmacokinetic analyses in section 12.0 
14. Updated the biomarker analyses in section 13.0 
15. Updated the biomarker listing in appendix 6 
5.6 Summary of Changes to Version 4.0 of SAP  
No analyses were performed prior to the revision of this SAP. 
1. Deleted “between visits as collected from ‘Rescue Medication’ eCRF page” in section 11.5.2 
6.0 Study Variables 
6.1 Efficacy Assessments 
The following efficacy procedures or tools will be used to assess subjects’ SLE disease activity during 
the study: 
British Isles Lupus Assessment Group (BILAG)-2004 
The BILAG-2004 grades are based on recording disease activity for 97 items in 9 different organ 
systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, 
gastrointestinal, ophthalmic, renal, and hematological, see Appendix 10 of the study protocol). Each 
item is measured qualitatively by clinical observation (yes/no, not present/improving/same/worse/new) 
based on lupus activity over the past 4 weeks compared with the previous 4 weeks or quantitatively by 
measuring hematologic and renal lab values. For abnormal lab values, the item is noted as SLE related 
or not SLE related. Based on scores of the 97 items, an alphabetical grade is derived for each organ 
system representing 5 levels of disease with A being the highest level of disease activity. The grades 
are given a numerical score equivalent: 
x 
A (very active) = 12 
x 
B (moderate disease activity) = 8 
x 
C (mild stable disease) = 1 
x 
D (no current disease activity but the system had previously been affected) = 0 
x 
E (no current or previous disease activity) = 0 
 
A global BILAG-2004 score (range from 0 to 108) is derived by summing-up the numerical score 
equivalents for each organ system. Grades are assigned by central reviewers 
 
 based on BILAG-2004 Index Scoring along with grading conventions. The detailed grading 
conventions are documented in the Central Review Plan including the handling of missing data when 
assigning the grades. Grades assigned in ‘BILAG Grading’ eCRF page will be used for analysis 
purpose.  
 
 
SLEDAI-2K 
The SLEDAI-2K is a global index based on weighted scores for each of 24 clinical findings rated as 
present or absent at the time of the visit or in the last 30 days (see Appendix 11 of the Study Protocol). 
The total score for SLEDAI-2K ranges from 0 to 105 with higher scores representing higher disease 
activity. The total score collected in ‘SLEDAI-2K’ eCRF page will be used for analyses. The detailed 
grading conventions are documented in the Central Review Plan including the handling of missing data 
when assigning the grades. 
 
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) 
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CLASI assesses cutaneous disease activity and damage by body surface area (see Appendix 12 of the 
study protocol). Only the CLASI activity score derived in ‘Cutaneous LE Disease Area and Severity 
Index (CLASI)’ eCRF page will be used in this study. 
For disease activity, points are given for presence of erythema, scale, hypertrophy, mucous membrane 
lesions, recent hair loss, and physician-observed alopecia and a total activity score is derived. The 
CLASI total activity score (CLASI-A) ranges from 0-70, where a higher score is associated with high 
disease activity. 
For the damage assessments, points are given for dyspigmentation, scarring, and scarring alopecia. A 
total damage score is derived. The CLASI total damage score (CLASI-D) ranges from 0 – 56, where a 
higher score is associated with larger extent of damage.   
40-joint Count 
Each of 40 joints is evaluated for the presence/absence of tenderness, swelling, and simultaneous 
presence/absence of both tenderness and swelling. The following joints will be evaluated: the 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). Bilateral first 
metacarpophalangeal joints and shoulders are also included, bringing the joint count to 40. From the 
above assessment, joint counts will be calculated for: 
x 
Tender joints (0-40) 
x 
Swollen joints (0-40) 
x 
Tender and swollen joints (0-40): joints that are both tender and swollen (= active) are counted. 
 
A larger joint count indicates more severe disease. The total joint counts collected from the eCRF will 
be used for analysis. 
Physician’s Global Assessment (PGA) of Disease Activity 
The Physician’s Global Assessment of Disease Activity (PGA) will be assessed using a 3-point visual 
analog scale (VAS) as the subject’s average disease activity over the past 30 days. A score of 0 
represents no disease activity and a score of 3 represents severe disease activity. An approximate 
score at tenth intervals between 0 and 3 (inclusive) will be reported. 
 
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6.2 Composite Measures 
The following composite measures will be determined based on assessments described above. 
BILAG-based Composite Lupus Assessment (BICLA) 
BICLA response is achieved if all of the following criteria are met: 
x 
Improvement in all organ systems with activity graded as BILAG-2004 A or B at baseline 
x 
No new organ system with activity graded as BILAG-2004 A and no more than 1 new organ 
system with activity graded as BILAG-2004 B since baseline 
x 
No increase from baseline in SLEDAI-2K (change from baseline of İ 0 score) 
x 
No increase from baseline ı 10% (or ı 0.3 points) in the Physician’s Global Assessment of 
Disease Activity on a 3-point VAS 
x 
No discontinuation of IP or use of restricted medications beyond the protocol allowed threshold 
before assessment (refer to section 11.7.2 with more details) 
 
SLE Responder Index (SRI[X]) 
The SRI is a composite responder endpoint. SRI(X) response is achieved if all of the following criteria 
are met: 
 
x 
5HGXFWLRQ IURP EDVHOLQH RI ; SRLQWV LQ WKH 6/('$,-2K 
x 
No new BILAG A (severe disease activity) and not more than 1 new BILAG B (moderate 
disease activity) organ domain grade since baseline 
x 
No worsening from baseline in the Physician’s Global Assessment of Disease Activity scale by 
> 0.3 points 
 
Lupus Low Disease Activity State (LLDAS) 
 
LLDAS response is achieved if all of the following criteria are met: 
 
x 
SLEDAI-.   ZLWK QR DFWLYLW\ LQ PDMRU RUJDQ V\VWHPV UHQDO FHQWUDO 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) 
x 
No new lupus disease activity compared with the previous assessment measured as no new 
or worsening individual BILAG parameters 
x 
3K\VLFLDQ¶V *OREDO $VVHVVPHQW RI 'LVHDVH $FWLYLW\   
x 
3UHGQLVRQH RU HTXLYDOHQW GRVH   PJGD\ 
x 
Well tolerated standard maintenance doses of immunosuppressive drugs and approved 
biologic agents (refer to section 11.7.2 with more details) 
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6.4 Safety 
Safety data to be collected includes physical examination and measurements, vital signs,12-lead ECG, 
hematology, clinical chemistry, urinalysis, coagulation, fasting lipid and glucose, pregnancy test results, 
concomitant medication use, and incidence and severity of all reported AE and SAEs. The planned time 
points for all safety assessments are listed in the Appendix 2. The change from baseline at each 
scheduled time point during the treatment period will be calculated for relevant measures. 
6.5 Predetermined Covariates and Prognostic Factors 
The following stratification factors are applied in this study: 
x 
CS dose (ı 10 mg/day or < 10 mg/day) 
x 
SLEDAI-2K score (ı 10 or < 10) 
x 
Region (North America, Latin America, Japan, rest of world) 
 
However, as CS dose and SLEDAI-2K score are not applied in Japan, the levels for the factor that is 
used in the analysis to represent the randomization strata is redefined as follows: 
 
1. CS dose = 'ı 10 mg/day', SLEDAI-2K score = 'ı 10', Region=þNorth Americaÿ; 
2. CS dose = 'ı 10 mg/day', SLEDAI-2K score = 'ı 10', Region=þLatin Americaÿ; 
3. CS dose = 'ı 10 mg/day', SLEDAI-2K score = 'ı 10', Region=þrest of worldÿ; 
4. CS dose = 'ı 10 mg/day', SLEDAI-2K score = '< 10', Region=þNorth Americaÿ; 
5. CS dose = 'ı 10 mg/day', SLEDAI-2K score = '< 10', Region=þLatin Americaÿ; 
6. CS dose = 'ı 10 mg/day', SLEDAI-2K score = '< 10', Region=þrest of worldÿ; 
7. CS dose = '< 10 mg/day', SLEDAI-2K score = 'ı 10', Region=þNorth Americaÿ; 
8. CS dose = '< 10 mg/day', SLEDAI-2K score = 'ı 10', Region=þLatin Americaÿ; 
9. CS dose = '< 10 mg/day', SLEDAI-2K score = 'ı 10', Region=þrest of worldÿ; 
10. CS dose = '< 10 mg/day', SLEDAI-2K score = '< 10', Region=‘North America’; 
11. CS dose = '< 10 mg/day', SLEDAI-2K score = '< 10', Region=‘Latin America’; 
12. CS dose = '< 10 mg/day', SLEDAI-2K score = '< 10', Region=‘rest of world’; 
13. CS dose = Not Applicable, SLEDAI-2K score = Not Applicable, Region=‘Japan’; 
 
The above redefined stratification factor collected from IVRS system will be included in statistical 
analysis models or be used to examine treatment effect. For subgroup analysis, the value of the above 
redefined stratification factor collected on the eCRF will be used. 
 
6.6 Pharmacokinetic and Pharmacodynamic Variables 
The pharmacokinetics of BMS-986165 and its metabolite BMT-153261 will be derived from plasma 
concentration versus time data. Biomarker data will be collected through serum, plasma, and urine 
samples to gain further understanding of the PD effects of BMS-986195. These samples will be 
analyzed for markers of tissue damage and regeneration including serum complement, anti-dsDNA and 
other autoantibodies, blood RNA for interferon-regulated gene (IRG) and steroid signature, genome-
wide expression, and inflammatory markers. 
 
Blood samples for pharmacokinetics and interferon-regulated gene (IRG) assessment will be collected 
predose and postdose at pre-specified study days and times. Actual sample times will be recorded and 
missed samples will be noted. 
 
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For a substudy of approximately 120 subjects, samples will be collected anytime on Days 2 and 3 for 
blood RNA and inflammatory markers.  
Blood flow cytometry data will also be collected in a substudy defined by geography and accessibility 
to the analyzing lab. Study will occur in USA and Europe. 
7.0 Definitions 
7.1 General 
The following data handling conventions will be used for general analysis: 
Term 
Definition 
Study Day 
The assessment date – date of first dose + 1. When the 
assessment date is before the date of first dose then study day 
is calculated as the assessment date - date of first dose. 
Baseline 
Baseline is defined as the last non-missing measurement prior 
to dosing on Day 1 (Week 0). If the measurement on Day 1 is 
missing or not available, then the last available measurement 
during the screening period will be used as a baseline.  
Baseline CS Dose Categorized 
For subjects taking CS at screening, the dose (prednisone or 
equivalent) must be stable for at least 2 weeks before the 
screening visit and must remain stable until randomization. The 
last CS dose during the screening period will be considered the 
baseline dose. For subjects not taking CS at screening, the 
baseline dose will be 0. Baseline CS Dose will be categorized as 
ı 10 mg/day or < 10 mg/day prednisone or equivalent for 
stratification. Baseline CS dose categorization will be from 
baseline CS dose eCRF form. 
Change from Baseline 
Change from baseline is defined as (value at post-baseline visit 
– value at baseline). 
Concomitant 
and 
Prior 
Medication 
Prior medications are defined as medications with a start or stop 
date prior to the first dose of study treatment. Concomitant 
medications are defined as any medication that occurred 
(continued, started, or stopped) on or after first dose of study 
medication and on or before last dose of study medication. 
End of Study (EOS) Date 
The EOS date is the date recorded on the eCRF that a 
randomized subject either discontinued or completed the study. 
If the subject is lost to follow-up, the EOS date will be the date of 
the last visit assessment obtained. 
First Dose Date 
The date a subject received their first dose on Day 1 as recorded 
in the ’Exposure - PK Sampling’ eCRF form, given that the first 
dose should be entered even if no PK sampling is collected at 
Day 1. Or if the first dose date is not collected in the ’Exposure - 
PK Sampling’ eCRF form, the   earliest   drug   dispensation date 
should be used. 
Last Dose Date 
The Date of Last Dose of Study Treatment on ‘End of Treatment’ 
eCRF form for a randomized subject. 
Percent Change from Baseline 
Percent change from baseline is defined as ([value at post-
baseline visit – value at baseline]/value at baseline) x 100. 
If the baseline value is 0 and the post-baseline value is also 0, 
then the percent change from baseline is set to 0. 
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7.2 Analysis Visits Windows 
Subjects do not always adhere strictly to the visit schedule timing in the protocol. Therefore, the 
designation of visits during the study period will be based on the day of evaluation relative to the Day 1 
of the trial (day of first dosing = study Day 1) rather than the nominal visit recorded in the case report 
form (CRF). Visit window based on the study day (regardless the visit labeling) will be applied for 
efficacy analysis and safety analysis. Each efficacy and safety measurement will be windowed. In case 
that two or more measurements exist in a certain visit window, the one closest to the target day will be 
selected. If still more than one measurements are selected, the later one will be selected for analysis.  
Efficacy measurements up to last dose will be used for windowing. 
Analysis Visit 
Target Day 
Study Day Range 
Baseline 
1 
[-28, 1] 
Week 2 
15 
[2, 22] 
Week 4 
29 
[23, 43] 
Week 8 
57 
[44, 71] 
Week 12 
85 
[72, 99] 
Week 16 
113 
[100, 127] 
Week 20 
141 
[128, 155] 
Week 24 
169 
[156, 183] 
Week 28 
197 
[184, 211] 
Week 32 
225 
[212, 239] 
Week 36 
253 
[240, 267] 
Week 40 
281 
[268, 295] 
Week 44 
309 
[296, 323] 
Week 48 
337 
[324, 351] 
Safety Follow-up 
EOT + 30 
 
 
8.0 Populations for Analyses 
The following populations will be used in the summary and analysis of study data. 
8.1 Enrolled 
The Enrolled population is defined as all subjects who signed informed consent. 
8.2 Randomized 
The Randomized population is defined as all subjects who are randomized to a treatment. Subjects will 
be analyzed as per randomized treatment according to the IRT. 
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8.3 All-treated 
The All-treated population consists of all randomized subjects who receive at least one dose of any 
study treatment. A subject will be considered to have received their randomized treatment unless they 
receive the incorrect treatment for the entire duration of the double-blind treatment period. 
8.4 Biomarker 
The Biomarker population is defined as all randomized subjects who receive at least one dose of study 
treatment and have at least one post-treatment biomarker measurement. Subjects will be analyzed 
according to the treatment received. 
8.5 Pharmacokinetic 
The Pharmacokinetic (PK) population is defined as all randomized subjects who receive at least one 
dose of BMS-986165 and have any available concentration data. The evaluable PK population is a 
subset of the PK Population that includes all subjects who have adequate PK profiles or have at least 
one evaluable PK parameter. 
The bioanalytical lab will receive the true randomization file and will only analyze the plasma samples 
from the subjects who received BMS-986165 drug. Subjects will be analyzed according to the treatment 
received. 
9.0 Analysis and Reporting 
The final (and only) database lock will occur once all randomized subjects have completed 48 weeks 
of double-blind treatment (or have discontinued earlier) and the 4-week safety follow-up for those who 
have not enrolled into the LTE study IM011074. 
10.0 Data Review 
10.1 Data Handling and Transfer 
Data will be entered and exported as SAS® version 9.4 or higher datasets. Converted datasets will be 
created using SAS® and following standard Clinical Data Interchange Standards Consortium Standard 
Data Tabulation Model (CDISC SDTM, version 1.4 or higher, Implementation Guide version v3.2 or 
higher) conventions. Analysis datasets will be created using SAS® and following CDISC Analysis Data 
Model (ADaM, version 2.1 or higher, Implementation Guide 1.1 standards or higher). 
Additional details can be found in the 
 Data Management Plan for this study. 
11.0 Statistical Methods 
Unless otherwise noted, variables will be reported using summary statistics according to the below 
methods by treatment group and analysis visit defined in section 7.2.    
Categorical variables will be summarized using frequency distributions (counts and percentages). 
Percentages will be rounded to one decimal place, and percentages will not be displayed for zero 
counts.  
For continuous variables summary statistics will include the number of observations (n), mean, standard 
deviation (SD), median, minimum, maximum, 25th percentile (Q1), and 75th percentile (Q3). The 
median, minimum, maximum, Q1, and Q3 values will be displayed to the same level of precision as the 
raw data, the mean to a further decimal place and the SD to two additional decimal places.  
P-values will be displayed to 3 decimal places, with values less than 0.001 presented as <0.001. 
All data will be listed by subject, analysis visit and treatment group. 
All statistical analysis and reporting will be done using SAS® Version 9.4 or higher (SAS Institute, Inc.). 
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11.1 Subject Disposition 
The number of subjects enrolled/screened, reasons of screen failure and the number and percentage 
of subjects randomized, treated, and in each analysis population will be presented.  
Additionally, the following summaries will be provided by treatment group and overall: 
x 
Number and percentage of subjects enrolled, randomized and treated by geographic region 
(North America, Latin America, Japan, rest of world), country, and center 
x 
Number and percentage of subjects who completed the study, discontinued the study, reason 
for study discontinuation, completed the treatment phase, discontinued treatments, and reason 
for treatment discontinuation 
x 
Number and percentage of subjects on treatment at each analysis visit 
Subject disposition data will be taken from the End Of Treatment and End Of Study CRF forms. 
 
11.2 Demographic and Baseline Characteristics 
Demographic characteristics will be reported by treatment group for both the randomized, and all-
treated populations using summary statistics. Demographic characteristics include the following: 
x 
Geographic Region (North America, Latin America, Japan, rest of world) 
x 
Sex 
x 
Race 
x 
Ethnicity 
x 
Age (in years, at time of signing informed consent) and age category (<65 vs ı65)  
x 
Baseline CS Use (yes, no) 
x 
Baseline Anti-malarial Use (yes, no) 
x 
Baseline Immunosuppressant Use (yes, no) 
x 
Oral CS Dose (observed dose as categories in mg/day, prednisone or equivalent) 
x 
Oral CS Dose (ı 10 mg/day vs < 10 mg/day; prednisone or equivalent) 
x 
Weight (in kg) 
x 
Height (in m) 
x 
Body mass index (BMI in kg/m2) 
x 
Number and percentage of subjects within each geographic region categorized by baseline CS 
dose (ı 10 mg/day or < 10 mg/day) and baseline SLEDAI-2K score (ı 10 or < 10) as collected 
on eCRF and on IRT 
 
The following baseline disease characteristics will be summarized by treatment group for the 
randomized population:  
 
x 
BILAG-2004 grade by organ system 
x 
BILAG-2004 global score 
x 
Categorization of BILAG-2004 A/B grades (at least one A, no A and at least 2 Bs, No A and < 
2 Bs) 
x 
SLEDAI-2K score 
x 
SLEDAI-2K (ı 10 or < 10) 
x 
CLASI-A score 
x 
swollen joint count 
x 
tender joint count 
x 
count of joints that are both tender and swollen (= active joints) 
x 
Physician’s Global Assessment of disease activity 
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11.3 Relevant Protocol Deviations 
Relevant protocol deviations considered to have a potential impact on the primary or key secondary 
efficacy endpoint assessments are: 
x 
Failure to meet any one or more inclusion criteria that define the patient population 
x 
Failure to adhere to concomitant medication restrictions affecting the primary endpoint 
x 
Poor compliance to study medication, i.e. overall compliance <75% for treatment period up to 
Week 32 
x 
Mis-dosed (treated dose not equal randomized dose) 
 
The detailed relevant protocol deviation criteria will be listed in Appendix 5.  
 
11.4 Exposure 
Summaries of extent of study drug exposure will be provided for the all-treated population. 
11.4.1 Duration of Exposure 
Duration of treatment will be calculated using the date of first dose of study drug and the date of last 
dose of study drug as recorded on the eCRF. Duration of treatment, in days, will be calculated according 
to the below formula: 
 
Date of last dose of study drug - date of first dose of study drug + 1 
Duration of treatment will be reported by treatment group using summary statistics. 
11.4.2 Summary of Dosing 
A single dose is defined as the randomized treatment dose. Subjects are to take a total of 8 capsules 
per day to equal one dose.  
The total number of doses taken for each subject will be determined as the following: 
Doses taken = (number capsules dispensed – number of capsules returned)/8 
The total number of doses taken will be reported using summary statistics by treatment group.  
11.4.3 Compliance 
 
Treatment compliance will be determined from data captured in the eCRF. 
The number and percentage of subjects who have missed at least one dose will be provided by 
treatment group. Additionally, summary statistics for the number of missed doses within each analysis 
visit period and overall will be provided by treatment group. The number of missed doses for each 
subject will be calculated as the following: 
( (8 x number of days in the analysis visit period) – (Number of capsules given – number of 
capsules returned) ) /8   
Overall compliance will be calculated based on eCRF data as specified below. 
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1. Number of doses taken = (number capsules dispensed – number of capsules returned)/8 
2. Number of expected doses taken = last dose date – first dose date + 1 
3. Compliance = (Number of doses taken / Number of expected doses taken) * 100 
If a subject does not return the container, then this dispensation event will be excluded in the calculation 
for the total number of doses taken, total number of expected doses, and total compliance. Overall 
compliance for the treatment period up to the Week 32 and up to Week 48 will be reported using 
summary statistics by treatment group and for the combined treatment groups. The number and 
percentage of subjects with <75%, 75% to 100%, and >100% compliance will be reported.  
11.5 Prior and Concomitant Medications 
Prior and concomitant medications will be coded according to World Health Organization-Drug 
Dictionary WHO-DD (June 2017 DDE HD B3 or an updated version at the time of database lock (DBL)) 
and will be summarized by Anatomic Therapeutic Classification (ATC) level 1, level 2 and preferred 
term (PT) by treatment group for the randomized population. The number and percentage of subjects 
using each medication will be displayed by treatment group. Subjects taking more than one medication 
within the same ATC level and/or PT will be counted once. Details of prescribing information will be 
provided in a listing. 
Medication dates will be imputed according to algorithms detailed in Appendix 3. The imputed dates will 
be used to assess whether medications should be included in the summaries as prior or concomitant, 
however the original, partial dates will be included in data listings. 
Only medications collected in the study database from first dose date of IP up to last dose day of IP or 
up to first dose day of study IM011-074 for roll over subjects will be summarized for concomitant 
medications. 
 
 
11.5.1 Prior Corticosteroid Use 
Prior systemic CS medications (prednisone or equivalent) will be summarized as described above for 
the number and percentage of subjects using each CS medication. A summary of other prior 
medications used for SLE may also be presented. 
The list of used CS medications to be selected for analyses is available in Appendix 6 of the protocol.  
Prior corticosteroid use data will be taken from the Prior and Concomitant Medications CRF form. 
 
11.5.2 Concomitant Corticosteroid Use 
Concomitant oral CS medications (prednisone or equivalent) will be summarized as described above 
for the number and percentage of subjects using each CS medication as well as continuous summaries 
of CS dose. The frequency and percentage of successful CS tapering and maintenance (defined as CS 
dose İ 7.5 mg/day prednisone or equivalent by Week 20 continuing through Week 32 and no CS 
rescue therapy) will be presented by treatment group as well a summary of the reasons CS was not 
reduced; due to a new or worse BILAG grade, a new or worse SLEDAI-2K score, new or worse 
hemolytic anemia, a CLASI-A score of at least 10, a tender and swollen joint count of at least 8, or 
others as collected on the Corticosteroid Dose Log CRF and Steroid Taper CRF forms. The need for 
CS rescue will be summarized with percentages of bursts <=1 or >1. A listing will provide details of CS 
therapy use throughout the study. A blinded review of the corticosteroid use will be conducted to assess 
whether a subject received a CS burst.  The logic for the determination of a CS burst and a spreadsheet 
with the CS bursts identified will be saved in the eTMF.  This spreadsheet will be used for programming 
of CS bursts. 
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The list of used CS medications to be selected for analyses is available in Appendix 6 of the protocol. 
Concomitant corticosteroid use data will be taken from the Corticosteroid Dose Log CRF forms. 
 
11.6 Medical History 
General medical history and medical history related to SLE will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA) (an updated version at the time of DBL). General medical history 
data will be summarized for each SOC and PT by treatment group and overall for the randomized 
population. Separate tables will be provided for general medical history and medical history related to 
SLE. Details of medical history will be provided in a listing. Medical history data will be taken from the 
General Medical History CRF. 
Additionally, BILAG SLE history (captured at screening) will be summarized for each body organ system 
by treatment group and overall for the randomized population. 
 
11.7 Efficacy Analyses 
All efficacy analyses will be performed using the randomized population.   
The final statistical analysis will be performed at the end of study after all subjects have completed their 
end of study visit (or discontinued early from the study). 
Separate methods will be used for binary, continuous, time-to-event and categorical efficacy endpoints.  
Subjects listings will report all collected efficacy endpoints over time until study end or early study 
discontinuation, regardless of treatment discontinuation before the study end or discontinuation. 
 
Binary endpoints for analysis are: 
x 
SRI(4)
 
x 
BICLA response 
x 
LLDAS response 
x 
CLASI-A response 
 
Continuous endpoints for analysis are: 
x 
Change from baseline in the 40-joint count for tender joints, swollen joints, and joints that are 
both tender and swollen (= active joints) 
x 
Global BILAG-2004 score 
Categorical endpoints: 
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11.7.1 Primary Endpoint 
The primary efficacy endpoint is the proportion of subjects who have a SRI(4) response at Week 32 
as per non-responder imputation. All subjects in the randomized population will be categorized as a 
responder or non-responder. 
Definition of Endpoint 
A responder is defined as meeting all of the following criteria. If one criterion is not met, the subject 
will be considered a non-responder. 
 
x 
Reduction from baseline of ı4 points in the SLEDAI-2K 
 
The total SLEDAI-2K score is the sum of the scores for all items. The total score will be taken 
from the eCRF. A reduction in at least 4 points is achieved if SLEDAI-2K at Week 32 – SLEDAI-
2K at baseline İ -4. 
 
x 
No new BILAG A (severe disease activity) and not more than 1 new BILAG B (moderate disease 
activity) organ domain grade 
 
An A grade is new if the baseline grade for the same organ system was B, C, D or E. A B grade 
is new if the baseline grade for the same organ system was C, D, or E. 
This criterion is met if both of the following conditions are met: 
o 
All organ domains with an A grade at Week 32 were graded A at baseline  
o 
The number of organ domains with a B grade at Week 32 that were graded C, D, or E 
at baseline is İ 1 
 
x 
No worsening from baseline in the Physician’s Global Assessment of Disease Activity scale by 
at least 0.3 points  
o 
Physician’s Global Assessment of Disease Activity at Week 32 – Baseline Physician’s 
Global Assessment of Disease Activity < 0.3 
 
Non-Responder Imputation (NRI) Method 
 
Subjects will be considered non-responders at a given time point per imputation (i.e. regardless of 
observed SRI-response as defined above) if any of the following apply: 
 
x 
Subject takes any of the following prohibited medications: 
o 
Corticosteroid dosages above 7.5mg/day prednisone or equivalent after week 20 
(Week 20+1 day) 
o 
Use of IM or IV CS within 8 weeks before the W32 assessment timepoint 
o 
Use of IA or intrabursal CS within 8 weeks before the W32 assessment timepoint 
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o 
Use of modified-release oral CS formulations within 8 weeks before the W32 
assessment timepoint 
o 
Addition (compared to baseline) of topical CS within 2 weeks before the W32 
assessment timepoint 
 
Ocular CS are allowed for non-SLE indications 
 
Inhaled CS are allowed 
o 
CS bursts/rescue above the protocol-defined maximum dosage (40 mg/day prednisone 
equivalent) 
o 
More than 1 CS burst or any CS burst for treatment of SLE after week 8 
 
Oral steroid burst for non-SLE indication is permitted up to week 24 or between 
week 32 and week 40 
o 
Initiation of or increases in oral NSAIDs (compared to baseline) occurring within the 7 
days before the W32 assessment timepoint 
o 
Initiation of or increase in immunosuppressant dosage/regimen and/or antimalarial 
dosage/regimen (compared to baseline) 
 
Dose decrease or discontinuation is permitted 
 
Discontinuation with subsequent restart at the same or lower doseis permitted 
 
Immunosuppressants are defined as (combinations of these are not 
permitted): Azathioprine, 6-MP, methotrexate, luflunomide, MMF 
 
Antimlalarials are defined as: chloroquine, hydroxychloroquine, or quinacrine 
x 
Subjects takes any medications included in protocol Appendix 7 between first dose date and 
efficacy assessment visit 
x 
Permanent treatment discontinuation of IP before the considered time point 
x 
Missing value for the endpoint at the considered time point 
x 
Subjects who are lost to follow-up or discontinue the study early are considered non-responders 
for all time points at and after loss to follow up or study discontinuation 
 
 
Primary Analysis 
 
The primary analysis will be conducted on the randomized population.  
The analysis of NRI-imputed SRI(4) response at Week 32 will be conducted using logistic regression 
modeling, with treatment group (four levels) and redefined stratification factor (see section 6.5, thirteen 
levels) as fixed factors. The odds ratios of response will be estimated and tested between the BMS-
986165 treatment groups and the placebo group
 
. In case the logistic regression model fit is not stable the 
region stratification factor may be removed from the model (resulting in 5 stratification factors: non-
Japan subjects with baseline CS dose   PJGD\ and SLEDAI-2K score  , non-Japan subjects 
with baseline CS dose < 10 mg/day and SLEDAI-2K score  , non-Japan subjects with CS dose  
mg/day and SLEDAI-2K score < 10, non-Japan subjects with CS dose < 10 mg/day and SLEDAI-2K 
score < 10 and Japan subjects). Estimated odds ratios of response with corresponding 2-sided 95% 
confidence interval (CI) and p-value will be reported.  
The number and percentage of subjects achieving NRI-imputed SRI(4) response at Week 32 and those 
who do not will be reported by treatment group with the estimated response rate and asymptotic 95% 
confidence intervals (CIs). Differences in response rates between each active treatment group and 
placebo with corresponding 2-sided 95% CIs based on the continuity-corrected Newcombe method will 
also be provided. 
 
Tipping Point Analysis 
Tipping point analysis will further be used to assess the robustness of the primary study results. 
Different number of events between treatment groups will be assessed until the study conclusion is 
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changed. Each imputed value is initially imputed as a responder. The imputed values in the placebo 
group will remain as responders while the BMS-986165 imputed values are replaced as a non-
responders one at a time, therefore changing the number of events between groups. Once all imputed 
values in the BMS-986165 group have been replaced with non-responders values, the data will reset 
to where the BMS-986165 group imputed values are all responders and one by one the imputed 
values in the placebo group are replaced with a non-responder until all placebo are non-responders 
and all BMS-986165 are responders. Furthermore, every pair of imputations between the placebo and 
BMS-986165 groups will be assessed similarly, creating a matrix of possible patterns.  
At each iteration, the statistical analysis is assessed, and the direction of the analysis is recorded. A 
graph will be provided to identify at what point to which the difference in events cause a direction shift 
in study results. The tipping point analyses will be based on a two-sample chi-square test approach 
rather than a stratified CMH test approach for simplicity of the analysis.  
 
 
Sensitivity analysis #1 (Treatment Policy Strategy) 
 
The primary analysis for the primary endpoint will be repeated using a treatment policy estimand 
approach (Intention-To-Treat (ITT) principle). For this approach, subjects will only be imputed as non-
responders if there is a missing value for the endpoint at the considered timepoint. 
 
Sensitivity analysis #2 
 
The primary analysis for the primary endpoint will be repeated, however the NRI imputation method will 
be modified. The prohibition medications restriction for the NRI imputation method will not apply. That 
is, subjects who take any of the prohibited medications listed above will not be imputed as non-
responders. Subjects will continue to be imputed as non-responders if any of the following apply:  
 
x 
Permanent treatment discontinuation of IP before the considered time point 
x 
Missing value for the endpoint at the considered time point 
x 
Subjects who are lost to follow-up or discontinue the study early are considered non-responders 
for all time points at and after loss to follow up or study discontinuation 
 
Supportive Analysis #1 – Assessment of Covid-19 related impact 
For this supportive analysis, the primary analysis for the primary endpoint will be repeated, but 
observations that were missed due to the impact of COVID-19 will be imputed with the last value 
observed before the visit that was missed due to COVID-19 restrictions. 
 
11.7.2 Secondary Endpoints 
11.7.2.1 SRI(4) Response at Week 48 
SRI(4) response at week 48 is defined in an analogous way as SRI(4) response at week 32 (see details 
in 12.7.1). 
Similar analyses will be conducted as for the primary endpoint, including the primary analysis and 
sensitivity analysis. 
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11.7.2.2 BICLA Response at Week 48 
All subjects in the randomized population will be categorized as a responder or non-responder. A 
subject will be considered a BICLA Week 48 responder if all of the following criteria are met. If one 
criterion is not met, the subject will be considered a BICLA Week 48 non-responder. 
x 
Improvement in all organ systems with activity graded as BILAG-2004 A or B at baseline 
 
o 
This criterion is met if both of the following conditions are met:All organ domains with 
an A grade at baseline are graded B, C, D, or E at Week 48  
o 
All organ domains with an B grade at baseline are graded C, D, or E at Week 48  
 
x 
No new organ system with activity graded as BILAG A and no more than 1 new organ system 
with activity graded as BILAG B 
An A grade is new if the baseline grade for the same organ system was B, C, D or E. A B grade 
is new if the baseline grade for the same organ system was C, D, or E. 
 
This criterion is met if both of the following conditions are met: 
o 
There are no organ domains with an A grade at Week 48  
o 
The number of organ domains with a B grade at Week 48 that were graded C, D, or E 
at baseline is İ 1 
 
x 
No increase from baseline in SLEDAI-2K (İ 0 points for change from baseline score) 
 
SLEDAI-2K score at Week 48 - SLEDAI-2K score at baseline İ 0 
 
x 
No increase ı 10% (or ı 0.3 points) in the Physician’s Global Assessment of Disease Activity 
on a 3-point VAS: 
 
Physician’s Global Assessment of Disease Activity at Week 48 – Baseline Physician’s Global 
Assessment of Disease Activity < 0.3 
 
x 
No discontinuation of IP or use of prohibited/restricted medications beyond the protocol allowed 
threshold before assessment.  
 
o 
No discontinuation of IP is defined as remaining on IP within 14 (İ 14) days prior to 
the Week 48 visit. Treatment discontinuation date is captured in the eCRF. 
o 
Restricted/prohibited medications are defined as in section 11.7.1 and are: 
 
Corticosteroid dosages above 7.5mg/day prednisone or equivalent after week 
20 (Week 20+1 day) 
 
Use of IM or IV CS within 8 weeks before the W32 and W48 assessment 
timepoints 
 
Use of IA or intrabursal CS within 8 weeks before the W32 and W48 
assessment timepoints 
 
Use of modified-release oral CS formulations within 8 weeks before the W32 
and W48 assessment timepoint 
 
Addition of topical CS within 2 weeks before the W32 and W48 assessment 
timepoint 
x 
Ocular CS are allowed for non-SLE indications 
x 
Inhaled CS are allowed 
 
More than 1 CS burst or any CS burst for treatment of SLE after week 8 
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x 
Oral steroid burst for non-SLE indication is permitted up to week 24 or 
between week 32 and week 40 
 
Initiation of or increases in oral NSAIDs occurring within the 7 days before the 
W32 and W48 assessment timepoints 
 
Initiation of or increase in immunosuppressant regimen and/or antimalarial 
dosage/regimen 
x 
Dose decrease or discontinuation is permitted 
x 
Discontinuation with restart at the same or lower dose is permitted 
x 
Immunosuppressants are defined as (combinations of these are not 
permitted): Azathioprine, 6-MP, methotrexate, luflunomide, MMF 
x 
Antimlalarials are defined as: chloroquine, hydroxychloroquine, or 
quinacrine 
o 
Any medications included in protocol Appendix 7 between first dose date and efficacy 
assessment visit 
 
 
Similar analyses will be conducted as for the primary endpoint, including the primary analysis and 
sensitivity analysis. 
11.7.2.3 CLASI-A Response (CLASI-50) at Week 48 
Subjects who have a baseline CLASI activity score ı10 will be included in this analysis. Subjects 
meeting this criterion will be categorized as CLASI-A responders or non-responders. Responders are 
defined as subjects who have at least a 50% decrease in their CLASI activity score at Week 48.  
CLASI activity score at Week 48– CLASI activity score at baseline
CLASI activity score at baseline
× 100 ൑െ50 
Subjects not meeting this criterion will be considered non-responders. 
Similar analyses will be conducted as for the primary endpoint, including the primary analysis and 
sensitivity analysis. 
11.7.2.4 LLDAS Response at Week 48 
A subject is considered an LLDAS responder at Week 48 if all of the following criteria are met: 
x 
SLEDAI-2K İ 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) 
 
This definition will be implemented as follows: 
o 
SLEDAI-2K İ 4  
o 
The following items on the SLEDAI-2K are scored as ‘no’: seizure, psychosis, organic 
brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, CVA 
(cerebrovascular accident), vasculitis, urinary casts, hematuria, proteinuria, pyuria, 
pleurisy, pericarditis, and fever 
o 
No hemolytic anemia on BILAG (item 96 on BILAG) 
o 
All BILAG gastrointestinal items scored as 0 (all items under gastrointestinal organ 
system graded D or E) 
 
x 
No new lupus disease activity compared with the previous assessment measured as no 
new or worsening individual BILAG parameter 
 
This definition will be implemented as follows: 
o 
None of the 97 BILAG items are scored 4 (=worse) or 5 (=new) 
o 
None of the 97 BILAG items are newly marked abnormal SLE related 
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If an item is rated Abnormal SLE Related at a visit then it must have been rated 
Abnormal SLE related at the previous visit. 
 
x 
Physician’s Global Assessment of Disease Activity İ 1 
x 
Prednisone or equivalent dose İ 7.5 mg/day 
x 
Well tolerated standard maintenance doses of immunosuppressive drugs and approved 
biologic agents 
 
Similar analyses will be conducted as for the primary endpoint, including the primary analysis and 
sensitivity analysis. 
11.7.2.5 Tender and Swollen Joint Count at Week 48 
The change from baseline in counts for tender, swollen, and tender + swollen (active) joints will be 
calculated on all subjects in the randomized population. 
x 
Tender 40-joint count at Week 48 – tender 40-joint count at baseline 
x 
Swollen 40-joint count at Week 48 – swollen 40-joint count at baseline 
x 
Tender + swollen (active) 40-joint count at Week 48 - tender + swollen 40-joint count at baseline 
 
Analyses of each of these three endpoints will be conducted using a mixed model repeated measures 
(MMRM) model. For analysis visits where the NRI-imputation criteria are met (see section 11.7.1), no 
imputation is applied but the observed values are set missing. The MMRM model will include the fixed 
categorical effects of treatment group, analysis visit (Week 24, 32 and 48), treatment-by-analysis visit 
interaction, randomization stratum defined in section 6.5 and the continuous fixed covariate of baseline 
endpoint. An unstructured covariance matrix will be used to model the correlation of the repeated 
measures within each subject. The parameter estimations will be based on the assumption of data 
being missing at random (MAR) and using the method of restricted maximum likelihood (REML). The 
denominator degrees of freedom will be calculated using the Kenward-Rogers method. Adjusted mean 
changes (LSMEANS) with corresponding SE and 95% CI per treatment arm will be reported. The 
difference in adjusted means (LSMEANS) between BMS-986165 and placebo at the predefined time 
point, and corresponding 95% CI and p-value based on this longitudinal repeated measures model will 
be provided. In case of non-convergence of the preferred longitudinal model, memory space issues, or 
other computational issues the following covariance structures will be used in order of preference 
(decreasing number of parameters to be estimated): heterogeneous toeplitz, heterogeneous compound 
symmetry, and compound symmetry. 
A longitudinal plot of mean change from baseline in tender joint count, swollen joint count, and tender 
+swollen joint count with standard errors by treatment group will be provided. 
 
A sensitivity analysis will be conducted similar to the primary endpoint (treatment policy strategy). 
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11.7.4 Subgroup Analysis 
Subgroup analyses will be performed for the primary endpoint, SRI(4) response at Week 32. Due to the 
reduced sample size within subgroup, no model-based adjusted odds ratios will be calculated. These 
analyses will include point estimates for response rate with asymptotic confidence intervals and the 
estimated unadjusted difference between study drug and placebo groups with Newcombe 95% 
confidence limits. P-values will not be reported for subgroup analyses. The following subgroups will be 
considered: 
x 
Baseline CS dose (< 10 mg/day, ı 10 mg/day) 
x 
Baseline SLEDAI-2K Score (< 10, ı 10) 
x 
Geographic region (North America, South America, Japan, rest of world) 
x 
Country 
x 
Gender (male, female) 
x 
Age group (18 - <45, 45 - <65, ı 65 years) 
x 
Weight (< median weight, ı median weight) 
x 
BMI (İ 30 kg/m2, > 30 kg/m2) 
x 
Race 
x 
Ethnicity (Hispanic or Latino, not Hispanic or Latino) 
x 
CS Use at baseline (yes, no) 
x 
Anti-malarial Use at baseline (yes, no) 
x 
Immunosuppressant Use at baseline (yes, no) 
x 
Interferon (IFN) status (high, low) 
x 
Years since initial diagnosis (<3 yrs, 3-6 yrs, >6 years)  
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11.8 Safety Analyses 
Safety summaries will be presented for the All-treated population, unless stated otherwise. 
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11.8.1 Adverse Events 
The collection of nonserious AE information begins at initiation of study treatment and continues until 
the last follow-up visit. All SAEs that occur from the time the informed consent form (ICF) is signed 
through 30 days after the final dose of the study treatment must be reported. After that time, only SAEs 
deemed by the investigator to be related to the study treatment or a study procedure would be reported. 
An adverse event (AE) including SAEs is defined as any new untoward medical occurrence or 
worsening of a preexisting medical condition in subjects that do not necessarily have causal relationship 
with treatment. Treatment-emergent adverse events (TEAEs) are those which first occur after the first 
dose of study drug or increase in severity after the first dose of study drug. The collected AEs (including 
SAEs) on CRF with an onset date between first dose date (including) and last dose day +30 days post 
last day or up to first dose day of study IM011-074 for roll over subjects will be summarized. All adverse 
events which change in severity or relationship to study drug are assigned a new start date and captured 
as a new record. 
AEs will be coded according to MedDRA (version 21.0 or an updated version at the time of DBL). All 
adverse event tables will be summarized by treatment group and combined BMS-986165 groups. 
A summary of the number and percentage of subjects reporting the following along with the number of 
events reported will be presented by treatment group and combined BMS-986165 groups: 
x 
Subjects with at least one treatment-emergent adverse event  
x 
Subjects with at least one treatment-related TEAE 
x 
Subjects with at least one serious adverse event 
x 
Subjects with at with one related serious adverse event 
x 
Subjects discontinuing study drug due to an adverse event 
x 
Subjects discontinuing study due to an adverse event  
x 
Subjects who died 
 
A breakdown of the number and percentage of subjects reporting each TEAE, categorized by coded 
body system and preferred term will be presented. Note that counting will be by subject not event and 
subjects are only counted once within each body system or preferred term; however, the number of 
total events including multiple events per subject will also be presented. A summary of treatment-related 
TEAEs will be provided. Furthermore, TEAEs and treatment-related TEAEs will be summarized for each 
preferred term in descending order. 
A summary of TEAEs categorized by severity (mild, moderate, or severe) will also be provided. Events 
reported under multiple categories will be considered only at their maximum severity. Subjects with 
multiple events within a particular body system or preferred term will be counted under the category of 
their most severe event within that body system or preferred term. 
A summary of TEAEs leading to discontinuation of study drug will be provided, grouped by body system 
and preferred term for all TEAEs and treatment-related TEAEs. 
All adverse events (including non-treatment-emergent events) recorded on the CRF will be listed. 
AE (including deaths) dates will be imputed according to algorithms detailed in Appendix 3. The imputed 
dates will be used to assess whether AEs should be considered as treatment-emergent and included 
in the safety summaries. The original, partial dates will be included in data listings. 
No imputation will be performed on missing AE severity or relationship, they will be left as missing. 
 
The exposure-adjusted incidence rate (EAIR) per 100 person-years of exposure (IR/100 P-Y) is 
calculated as follows: 
100 (݌݁ݎݏ݋݊) כ  
number of subjects with the specific event
total exposure-time (in years) among the subjects of that particular treatment 
where total exposure time (years) among the subjects of that particular treatment 
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= ¦ (݁ݔ݌݋ݏݑݎ݁ ݐ݅݉݁ (݀ܽݕݏ) ݂݋ݎ ݈݈ܽ ݏݑܾ݆݁ܿݐݏ ݋݂ ݐ݄ܽݐ ݌ܽݎݐ݅ܿݑ݈ܽݎ ݐݎ݁ܽݐ݉݁݊ݐ) כ
 ଵ ௬௘௔௥
ଷ଺ହ.ଶହ ௗ௔௬௦  
Subject Exposure Time (days) is calculated as follows: 
- 
If a subject has at least 1 event while on that particular treatment, the exposure time for that 
subject is: 
First AE onset date – Treatment start date (of that particular treatment) + 1 day 
 
- 
If a subject does not have an event, the exposure time for that subject is:  
Treatment stop date (of that particular treatment) – Treatment start date (of that particular 
treatment) + 1 day 
 
11.8.2 Adverse Events of Interest 
Adverse events of interest (AEI) include the following: 
x 
Skin-related AEs 
x 
Influenza 
x 
Herpes Zoster 
x 
Tuberculosis 
x 
Opportunistic/Other Infections 
x 
Malignancy events 
 
These events will be summarized by body system and preferred term. cSMQ defined at program level 
will be applied to select the AEIs.  
Creatine kinase (CK) elevation for CK elevation > 2.5 upper limit of normal will be summarized as 
CTCAE grade 2 or higher in the clinical laboratory summaries. 
11.8.3 Deaths and Serious Adverse Events 
The number and percentage of subjects reporting each SAE, categorized by body system and preferred 
term coded will be presented. Note that counting will be by subject not event and subjects are only 
counted once within each body system or preferred term; however, the number of total events including 
multiple events per subject will also be presented. A further tabulation of these events if related to the 
study drug, as reported on the CRF, will be provided.  
All SAEs will be provided in a listing. 
Adverse events with an outcome of death will be summarized.  
All AEs with an outcome of death will be listed for the enrolled population. 
11.8.4 Laboratory Data 
Laboratory parameters will be summarized using both the International System (SI) of Units and 
conventional system of Units, unless otherwise specified. Summaries will be provided separately by 
different panels including hematology, general chemistry, chemistry - hepatobiliary, chemistry - renal 
function tests, chemistry - coagulation, and urinalysis. Only lab assessments with collection date up to 
last dose day +30 days post last dose day or up to first dose day of study IM011-074 for roll over 
subjects will be summarized. Data will be summarized by analysis visit, as applicable. The following 
summaries will be provided for each parameter: 
o 
Absolute and change from baseline values 
o 
Laboratory abnormalities (as determined by Controlled Terminology Criteria for 
Adverse Events [CTCAE v5.0] grading) presented as the worst postbaseline toxicity 
group 
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o 
Shifts from baseline to maximum postbaseline value 
o 
Potential drug induced liver injury (DILI) is defined as a subject who meets the following 
criteria on the same assessment date: 
 
1) ALT or AST elevation >3 times ULN 
AND 
 
2) Total bilirubin >2 times ULN  
AND 
 
Normal serum alkaline phosphatase (No initial findings of cholestasis) 
o ALT or AST elevation >5 times ULN 
 
x 
All abnormalities in laboratory data will be provided in listings. 
11.8.5 Vital Signs 
Vital signs including body temperature, respiratory rate, systolic blood pressure (SBP) and diastolic 
blood pressure (DBP), and heart rate will be listed. Absolute lab values, change from baseline values 
will be reported with summary statistics by treatment group and analysis visit. 
The summaries of marked abnormalities at any timepoint postbaseline will also be tabulated for 
definitions provided as below.  
o 
Absolute and change from baseline values 
o 
Marked abnormalities defined by the below categories: 
 
Heart rate: 
x 
Value > 100 and change from baseline > 30 
x 
Value < 55 and change from baseline < -15 
 
Systolic blood pressure: 
x 
Value > 140 and change from baseline > 20 
x 
Value < 90 and change from baseline < -20 
 
Diastolic blood pressure: 
x 
Value > 90 and change from baseline > 10 
x 
Value < 55 and change from baseline < -10 
 
11.8.6 ECG 
Summary statistics will be presented for ECG observed values, change from baseline values for all 
ECG parameters by treatment group and analysis visit. 
 
The summaries of marked abnormalities at any timepoint post-baseline will also be tabulated for 
definitions provided as below. 
o 
Absolute and change from baseline values 
o 
Marked abnormalities defined by the below categories: 
 
QT interval corrected using Fridericia’s formula (QTcF): 
x 
450 -< 480 msec 
x 
480 -< 500 msec 
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x 
ı 500 msec 
x 
30 < change from baseline İ 60 msec 
x 
Change from baseline > 60 msec 
x 
Males: < 450 msec, ı 450 msec 
x 
Females: < 470 msec, ı 470 msec 
 
PR interval ı 200 msec 
 
QRS interval ı 200 msec 
In cases where QTcF is missing, then QTcF will be derived using the following definition: QTcF = QT/ ( 
RR^(1/3) ), where RR (seconds) =  60 / HR. In case where both QTcF and QT are missing, then QTcF 
will be derived using the following definition: QTcF = QTcB/ ( RR^(1/6) ), where RR (seconds) =  60 / 
HR. 
 
Additionally, all ECG data will be provided in a listing. 
11.8.7 Physical Examination 
Complete physical examinations results will be summarized using frequency distributions for each body 
system by treatment group and analysis visit. 
 
All physical examination results will be provided in a listing.  
 
11.9 Statistical impacts due to Covid-19 
 
11.9.1 Impact on efficacy endpoints 
 
Some subjects in this study did not complete all planned visits due to the impact of COVID-19, which 
can potentially impact the primary and secondary efficacy endpoints. It is plausible to assume that the 
underlying missingness mechanism due to the COVID-19 is ‘missing at random (MAR)’. Based on that 
assumption, the following approaches will be applied: 
- 
For statistical analyses that are based on methods that are in agreement with the MAR assumption 
(e.g. MMRM model for continuous endpoints), the point estimates of treatment-specific means and 
differences can be assumed not be affected. Therefore, no modifications will be done to these 
analyses and no additional analyses will be conducted to address it. 
- 
For statistical analyses that implement a missing-not-at-random imputation strategy (e.g. NRI for 
binary endpoints), estimated treatment-specific means and differences could be affected if the 
frequency of COVID-19 related missing observations differs between treatment groups. Therefore, 
for binary endpoints, a sensitivity analysis will be conducted where observations that were missed 
due to COVID-19 will be imputed with the last value observed before the visit that was missed due 
to COVID-19 restrictions  
11.9.2 Impact on safety endpoints 
No modifications will be made for the analysis of safety data due to COVID-19-related issues. There 
will not be any additional safety data handling considerations for missing data or treatment interruptions 
due to COVID-19. 
 
 
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12.0 Pharmacokinetic Analysis 
The Pharmacokinetic (PK) population will be used for all listings. The Evaluable PK population will be 
used for summaries and statistical analyses. 
12.1 Plasma Concentrations 
PK concentrations of BMS-986165 and BMT-153261 will be listed by subject and treatment at each 
scheduled time point. 
The following groups will be summarized: 
x 
Subjects who received 12 mg BMS-986165 QD 
x 
Subjects who received 6 mg BMS-986165 BID 
x 
Subjects who received 3 mg BMS-986165 BID 
 
For the summaries of concentration-time data, concentrations that are less than the lower limit of 
quantification (LLOQ) should be displayed as “< LLOQ” in the listings and be treated as missing.  
Summaries of plasma concentrations of BMS-986165 and BMT-153261 will be provided for the PK 
population by day and scheduled time point as outlined above using summary statistics (n, mean, SD, 
geometric mean, %CV, median, min, max).  
 
 
12.2 Pharmacokinetic Parameters 
The following PK parameters may be estimated for BMS-986165 and the active metabolite BMT-153261 
using noncompartmental methods by a validated PK analysis program, if data permits. 
 
 
All individual PK parameters will be listed for each analyte. Summaries of PK parameters will be 
tabulated for each analyte by treatment using descriptive statistics (n, mean, SD, median, min, max, 
geometric mean, and %CV). 
The plasma PK parameters will be estimated from the concentration-time profiles. For the purpose of 
calculating PK parameters except Ctrough, predose concentrations below the lower limit of quantitation 
(<LLOQ) and concentrations prior to the first quantifiable concentration that were <LLOQ were set to 
“zero,” all other <LLOQ concentrations were set to “missing.” Actual sampling times, rather than 
scheduled sampling times, will be used in all computations involving sampling times.  
Only true trough concentrations will be summarized. True trough concentrations are defined as PK 
concentrations measured before the next dose within the window of 24 hrs +/- 4 hrs for QD dosing and 
12 hrs +/- 2 hrs for BID dosing. Samples taken accidentally after the dose occurred as well as samples 
taken earlier than specified windows will not be included in summaries. 
Parameter 
Description 
Plasma PK Parameters 
Cmax 
Maximum observed concentration, obtained directly from the experimental data without 
interpolation, expressed in concentration units determined on Day 85. 
 
Tmax 
Time of maximum observed plasma concentration associated with Cmax on Day 85 
Ctrough 
Observed predose (trough) concentration determined on Days 15, 29, 57, 85, 169, 
225, and 337. 
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Summary statistics for Ctrough concentrations will be calculated by imputing values less than LLOQ as 
½ × LLOQ. This imputation is performed for Ctrough concentrations and not conducted for Day 1 pre-
dose concentrations. Individual Ctrough listings will display these concentrations as “< LLOQ.” 
The comparison of trough concentrations of parent drug and metabolite(s) for all 3 groups will be 
presented graphically in the box/scatter plots.  
 
13.0 Biomarker Analysis 
Summaries will be provided for the biomarker analysis population. Summaries include mean, SD, 
median, IQR, range, change from baseline and percent change from baseline. Summaries for the 
following biomarkers will be provided for treatment arms as well as for baseline IFN status (IFN-high 
and IFN-low) under each arm at each analysis visit. IFN-high vs. IFN-low will be designated based on 
IFN evaluation of samples collected during the screening period. Demographic information of subjects 
for each IFN status will be provided. 
x 
aggregated genes (IRGs
)  
x 
clinical markers: C3, C4, Coomb’s test, anti-dsDN
% Change of individual IRGs will be derived as follows:  
x 
The log2 Fold Change of each gene of each subject = [normalized log2 value at time point]- 
[normalized log2 value at Day 1 predose] 
x 
% Change from Baseline of each gene at a time point = [2^(log2 Fold Change)-1] x 100 
 
 
14.0 Interim Analysis 
No interim analysis will be performed during the course of the study. 
 
 
15.0 References 
 
Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative 
PCR and the 2-ǻǻCT Method. Methods. 25(4):402-8 
Greenland and Mansournia (2015). Penalization, Bias reduction, and default priors in logistic and 
related categorical and survival regressions. Statistics in Medicine 34, 3133-3143 
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. 
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Appendix 1 Glossary of Abbreviations 
 
Glossary of Abbreviations: 
ACR 
American College of Rheumatology 
AE 
Adverse Event 
AEI 
Adverse Events of Interest 
ATC 
Anatomic Therapeutic Classification 
BICLA 
British Isles Lupus Assessment Group-based Composite Lupus 
Assessment 
BILAG 
British Isles Lupus Assessment Group 
CI 
Confidence Interval 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CRF 
Case Report Form 
CRP 
C-reactive Protein 
CS 
Corticosteroid 
CSR 
Clinical Study Report 
DBL 
Database Lock 
DBP 
Diastolic Blood Pressure 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
EOS 
End-Of-Study 
ESR 
Erythrocyte Sedimentation Rate 
FP 
Follow up Period 
IFN 
Interferon 
IRG 
Interferon-Regulated Gene 
IRT 
Interactive Response Technology 
IVRS 
Interactive Voice Response System 
LLDAS 
Lupus Low Disease Activity State 
LS 
Least Square 
NSAID 
Nonsteroidal Anti-Inflammatory Drug 
MedDRA 
Medical Dictionary for Regulatory Activities 
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PCI 
Potentially Clinically Important 
PGA 
Physician’s Global Assessment 
PK 
Pharmacokinetic 
PPS 
Per Protocol Set 
SAP 
Statistical Analysis Plan 
SAE 
Serious Adverse Event 
SBP 
Systolic Blood Pressure 
SLE 
Systemic Lupus Erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SP 
Study Period 
SRI(X) 
6\VWHPLF /XSXV (U\WKHPDWRVXV 5HVSRQGHU ,QGH[ RI  X 
TB 
Tuberculosis 
Tyk2 
Tyrosine Kinase 2 
VAS 
Visual Analog Scale 
WHO 
World Health Organization 
 
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Appendix 2 Schedule of On-Treatment Activities 
 
Treatment Period Procedural Outline Up to Week 24 
Procedure 
Week 0 
D1 
Week 2 
D15 
(±3 d) 
Week 4 
D29 
(±3 d) 
Week 8 
D57 
(±3 d) 
Week 12 
D85 
(±3 d) 
Week 16 
D113 
(±3 d) 
Week 20 
D141 
(±3 d) 
Week 24 
D169 
(±3 d) 
Eligibility/randomization criteria 
X 
 
 
 
 
 
 
 
Safety Assessments 
 
 
 
 
 
 
 
 
Complete PE 
X 
 
 
 
 
 
 
 
Targeted PE 
 
X 
X 
X 
X 
X 
X 
X 
Body weight 
X 
 
X 
X 
X 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogram 
X 
 
X 
X 
X 
 
 
 
Concomitant medication use 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor for AEs and SAEs 
X 
 
 
 
 
 
 
X 
Laboratory Tests 
 
 
 
 
 
 
 
 
Hematology, chemistry, urinalysis, 
coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
Fasting lipid panel 
X 
 
 
 
X 
 
 
 
Fasting plasma glucose 
X 
 
 
 
X 
 
 
 
Pregnancy test (WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
X 
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Procedure 
Week 0 
D1 
Week 2 
D15 
(±3 d) 
Week 4 
D29 
(±3 d) 
Week 8 
D57 
(±3 d) 
Week 12 
D85 
(±3 d) 
Week 16 
D113 
(±3 d) 
Week 20 
D141 
(±3 d) 
Week 24 
D169 
(±3 d) 
Spot urine for protein creatinine ratio 
X 
 
X 
X 
X 
X 
X 
X 
Coomb’s Test (direct) 
X 
 
X 
X 
X 
X 
X 
X 
hsCRP 
X 
 
 
 
X 
 
 
X 
TBNK 
X 
 
 
 
X 
 
 
X 
Serum Ig 
X 
 
X 
 
X 
 
 
X 
PK Assessments 
X 
X 
X 
X 
X 
 
 
X 
Biomarker Assessments 
 
 
 
 
 
 
 
 
Serum Complement 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-dsDNA autoantibodies 
X 
 
X 
X 
X 
X 
X 
X 
Blood RNA for IRG and steroid signature, 
and genome-wide expression 
X 
X 
X 
X 
X 
X 
X 
X 
Efficacy Assessments 
 
 
 
 
 
 
 
 
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Procedure 
Week 0 
D1 
Week 2 
D15 
(±3 d) 
Week 4 
D29 
(±3 d) 
Week 8 
D57 
(±3 d) 
Week 12 
D85 
(±3 d) 
Week 16 
D113 
(±3 d) 
Week 20 
D141 
(±3 d) 
Week 24 
D169 
(±3 d) 
BILAG-2004 Index 
X 
 
X 
X 
X 
X 
X 
X 
SLEDAI-2K 
X 
 
X 
X 
X 
X 
X 
X 
Physician’s Global Assessment 
X 
 
X 
X 
X 
X 
X 
X 
40-joint count 
X 
 
X 
X 
X 
X 
X 
X 
CLASI 
X 
 
X 
X 
X 
X 
X 
X 
Photography 
X 
 
X 
X 
X 
X 
X 
X 
Assess suitability for CS taper 
(X) 
(X) 
(X) 
X 
X 
X 
X 
 
Patient’s Global Assessment 
X 
 
X 
X 
X 
X 
X 
X 
Pain assessment 
X 
 
X 
X 
X 
X 
X 
X 
Clinical Drug Supplies 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
Dispense Study Treatment 
X 
 
 
 
 
 
 
X 
Study Treatment Administration 
X 
 
 
 
 
 
 
X 
Study Treatment Compliance 
 
X 
X 
X 
X 
X 
X 
X 
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Treatment Period Procedural Outline After Week 24 
Procedure 
Week 28 
D197 
(±3 d) 
Week 32 
D225 
(±3 d) 
Week 36 
D253 
(±3 d) 
Week 40 
D281 
(±3 d) 
Week 44 
D309 
(±3 d) 
Week 48 
D337/EOT 
(±3 d) 
FP 
(28 days after 
EOT)a 
Safety Assessments 
 
 
 
 
 
 
 
Complete PE 
 
X 
 
 
 
X 
 
Targeted PE 
X 
 
X 
X 
X 
 
X 
Body weight 
X 
X 
X 
X 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogram 
 
X 
 
 
 
X 
 
Concomitant medication use 
X 
X 
X 
X 
X 
X 
X 
Monitor for AEs and SAEs 
X 
 
 
 
 
 
X 
Laboratory Tests 
 
 
 
 
 
 
 
Hematology, chemistry, urinalysis, 
coagulation 
X 
X 
X 
X 
X 
X 
X 
Fasting lipid panel 
 
X 
 
 
 
X 
 
Fasting plasma glucose 
 
X 
 
 
 
X 
 
Pregnancy test (WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
Spot urine for protein creatinine ratio 
X 
X 
X 
X 
X 
X 
X 
Coomb’s Test (direct) 
X 
X 
X 
X 
X 
X 
X 
hsCRP 
 
X 
 
X 
 
X 
 
TBNK 
 
X 
 
 
 
X 
 
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Procedure 
Week 28 
D197 
(±3 d) 
Week 32 
D225 
(±3 d) 
Week 36 
D253 
(±3 d) 
Week 40 
D281 
(±3 d) 
Week 44 
D309 
(±3 d) 
Week 48 
D337/EOT 
(±3 d) 
FP 
(28 days after 
EOT)a 
Serum Ig 
 
X 
 
 
 
X 
X 
PK Assessments 
 
X 
 
 
 
X 
 
Biomarker Assessments 
 
 
 
 
 
 
 
Serum Complement 
X 
X 
X 
X 
X 
X 
X 
Anti-dsDNA autoantibodies 
X 
X 
X 
X 
X 
X 
X 
Blood RNA for IRG, steroid signature, 
and genome-wide expression 
X 
X 
X 
X 
X 
X 
X 
Efficacy Assessments 
 
 
 
 
 
 
 
BILAG-2004 Index 
X 
X 
X 
X 
X 
X 
X 
SLEDAI-2K 
X 
X 
X 
X 
X 
X 
X 
Physician’s Global Assessment 
X 
X 
X 
X 
X 
X 
X 
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Procedure 
Week 28 
D197 
(±3 d) 
Week 32 
D225 
(±3 d) 
Week 36 
D253 
(±3 d) 
Week 40 
D281 
(±3 d) 
Week 44 
D309 
(±3 d) 
Week 48 
D337/EOT 
(±3 d) 
FP 
(28 days after 
EOT)a 
40-joint count 
X 
X 
X 
X 
X 
X 
X 
CLASI 
X 
X 
X 
X 
X 
X 
X 
Photography 
X 
X 
X 
X 
X 
X 
X 
Assess suitability for CS taper 
 
X 
X 
X 
 
X 
 
Patient’s Global Assessment 
X 
X 
X 
X 
X 
X 
X 
Pain assessment 
X 
X 
X 
X 
X 
X 
X 
Clinical Drug Supplies 
 
 
 
 
 
 
 
Dispense Study Treatment 
X 
X 
X 
X 
X 
 
 
Study Treatment Administration 
X 
X 
X 
X 
X 
X 
 
Study Treatment Compliance 
X 
X 
X 
X 
X 
X 
 
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Appendix 3 Imputation Rules for Partial of Missing Dates 
 
Start Date 
Stop Date 
Complete: 
yyyymmdd 
Partial: yyyymm 
Partial: yyyy 
Missing/
Ongoing 
<1st 
dose 
st 
dose 
<1st dose 
yyyymm 
st dose 
yyyymm 
<1st dose 
yyyy 
st dose 
yyyy 
Partial: 
yyyymm 
= 1st dose 
yyyymm 
2 
1 
n/a 
1 
n/a 
1 
1 
 st dose 
yyyymm 
2 
2 
2 
2 
2 
2 
Partial: 
yyyy 
= 1st dose 
yyyy 
3 
1 
3 
1 
n/a 
1 
1 
 st dose 
yyyy 
3 
3 
3 
3 
3 
Missing 
4 
1 
4 
1 
4 
1 
1 
1 = Impute as the date of first dose 
2 = Impute as the first of the month 
3 = Impute as January 1 of the year 
4 = Impute as January 1 of the stop year 
Note: If the start date imputation leads to a start date that is after the stop date, then there is a data error 
and do not impute the start date. 
Imputation rules for partial or missing stop dates: 
1. Initial imputation 
a. For partial stop date “mmyyyy”, impute the last of the month. 
b. For partial stop date “yyyy”, impute December 31 of the year. 
c. For completely missing stop date, do not impute. 
2. If the stop date imputation leads to a stop date that is after the death date, then impute the 
stop date as the death date. 
3. If the stop date imputation leads to a stop date that is before the start date, then there is a 
data error and do not impute the stop date. 
Imputation rules for partial or missing death dates: 
1. If death year and month are available but day is missing: 
a. If “mmyyyy” for last contact date = “mmyyyy” for death date, set death date to the day 
after the last contact date. 
b. If “mmyyyy” for last contact date < “mmyyyy” for death date, set death date to the first 
day of the death month. 
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c. If “mmyyyy” for last contact date > “mmyyyy” for death date, data error and do not 
impute. 
2. If both month and day are missing for death date or a death date is totally missing, set death 
date to the day after the last contact date. 
 
 
 
 
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Appendix 5 Relevant Programmable PDs 
 
 
x 
Eligibility Deviations: 
- 
Subjects were not GLDJQRVHG   ZHHNV EHIRUH WKH VFUHHQLQJ YLVLW  
- 
Subjects did not meet SLICC classification 
- 
Subjects did not meet at least one of the following serology criteria: 
 
HOHYDWHG DQWLQXFOHDU DQWLERGLHV $1$  , or positive anti-dsDNA (positive includes 
indeterminate results), or positive anti-Smith (anti-Sm) as determined by the central laboratory 
- 
Subjects did not meet BILAG grading criteria 
- 
Subjects did not meet SLEDAI-2K criteria 
- 
Subjects did not meet background meds requirements for immunosuppressants, antimalarials 
(must be on one of these med type, no dose requirements) based on a list of WHO Drug coding 
terms 
- 
For subjects receiving prednisone or equivalent, the dose of CS was not stable for 2 weeks before 
the screening visit (signing of informed consent) or throughout the screening period until 
randomization  
- 
A more than 30 mg/day prednisone or equivalent dose was used during the screening period (or in 
the 2 weeks preceeding the screening visit)  
- 
Subjects have drug induced lupus, other autoimmune diseases, SLE overlap syndromes   
Note: All eligibility related relevant PDs will be determined based on data collected from Eligibility – 
Screening eCRF page and assessments on day 1  
x 
Incorrect dosing: 
- 
Subjects took medication other than randomized treatment for the entire duration of the study. 
- 
Overall compliance <75% for the treatment period to Week 32. 
x 
Restricted and Prohibited medications: 
- 
Subjects should not take any medications included in protocol Appendix 7 between first dose and 
efficacy assessment. A list of WHO Drug coding terms will be defined at protocol level.  
- 
Subjects who take any prohibited medications listed in section 11.7.1 
 
 
 
Appendix 6 List of Biomarkers 
 
Interferon regulated genes (IRGs) 
HERC5* 
IRF7 
MX1* 
CXCL10 
STAT2 
DDX58 
DHX58 
EIF2AK2 
IFI44* 
IFI44L* 
IFIT1* 
ISG15* 
LGALS3BP  
PARP9 
RSAD2* 
TNFSF13B  
 
 
 
 
Approved
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Approved
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Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 58 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
Approved
3.0
v
Approved
1.0
v


 
Statistical Analysis Plan 
Version Date: 20-DEC-2021 
Sponsor: Bristol-Myers Squibb 
Protocol no: IM011021 
 
Page 59 of 59 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
Approved
3.0
v
Approved
1.0
v