A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in Patients With Systemic Lupus Erythematosus
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Sponsor: Eli Lilly and Company

Protocol I4V-MC-JAIA(b) 
 
 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib 
in Patients with Systemic Lupus Erythematosus 
 
NCT03616964 
 
Approval Date: 20-Apr-2020 
 
 

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Protocol I4V-MC-JAIA(b)
A Randomized, Double-Blind, Placebo-Controlled, 
Parallel-Group, Phase 3 Study of Baricitinib in Patients 
with Systemic Lupus Erythematosus
EUDRA CTA 2017-005027-25
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of
baricitinib (LY3009104), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Baricitinib (LY3009104)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly: 26 April 2018
Amendment (a) Electronically Signed and Approved by Lilly:  07 December 2018
Amendment (b) Electronically Signed and Approved by Lilly
on approval date provided below.
Approval Date: 20-Apr-2020 GMT

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Table of Contents
Section
Page
Protocol I4V-MC-JAIA(b) A Randomized, Double-Blind, 
Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib in 
Patients with Systemic Lupus Erythematosus......................................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................13
3.
Introduction ......................................................................................................................22
3.1.
Study Rationale............................................................................................................22
3.2.
Background..................................................................................................................23
3.3.
Benefit/Risk Assessment..............................................................................................24
4.
Objectives and Endpoints..................................................................................................27
5.
Study Design.....................................................................................................................31
5.1.
Overall Design .............................................................................................................31
5.2.
Number of Participants.................................................................................................33
5.3.
End of Study Definition ...............................................................................................33
5.4.
Scientific Rationale for Study Design...........................................................................33
5.5.
Justification for Dose ...................................................................................................34
6.
Study Population...............................................................................................................36
6.1.
Inclusion Criteria..........................................................................................................36
6.2.
Exclusion Criteria ........................................................................................................39
6.3.
Lifestyle Restrictions....................................................................................................44
6.4.
Screen Failures.............................................................................................................44
7.
Treatments........................................................................................................................45
7.1.
Treatments Administered .............................................................................................45
7.1.1.
Packaging and Labelling ......................................................................................45
7.2.
Method of Treatment Assignment ................................................................................46
7.2.1.
Selection and Timing of Doses.............................................................................46
7.2.2.
Dose Adjustment for Renal Impairment ...............................................................46
7.3.
Blinding .......................................................................................................................47
7.4.
Dosage Modification....................................................................................................47
7.5.
Preparation/Handling/Storage/Accountability...............................................................47
7.6.
Treatment Compliance .................................................................................................47
7.7.
Concomitant Therapy...................................................................................................48
7.7.1.
Permitted Changes and Additions to Concomitant Therapy..................................49

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7.7.2.
Prohibited Changes in Concomitant Therapy........................................................49
7.8.
Treatment after the End of the Study............................................................................50
7.8.1.
Study Extensions..................................................................................................50
7.8.2.
Treatment after Study Completion........................................................................50
8.
Discontinuation Criteria ....................................................................................................51
8.1.
Discontinuation from Study Treatment.........................................................................51
8.1.1.
Temporary Interruption of Investigational Product ...............................................51
8.1.2.
Permanent Discontinuation from Study Treatment ...............................................52
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................54
8.2.
Discontinuation from the Study....................................................................................54
8.3.
Lost to Follow-up.........................................................................................................55
9.
Study Assessments and Procedures ...................................................................................56
9.1.
Efficacy Assessments...................................................................................................56
9.1.1.
Primary Efficacy Assessment...............................................................................56
9.1.1.1.
Systemic Lupus Erythematosus Disease Activity 
Index-2000 .....................................................................................................56
9.1.1.2.
British Isles Lupus Assessment Group 2004 Index..........................................56
9.1.1.3.
Physician’s Global Assessment of Disease Activity........................................57
9.1.2.
Secondary and Exploratory Efficacy Assessments................................................57
9.1.2.1.
Systemic Lupus Erythematosus Responder Index ...........................................57
9.1.2.2.
Systemic Lupus Erythematosus Disease Activity 
Index-2000 .....................................................................................................57
9.1.2.3.
British Isles Lupus Assessment Group 2004 Index..........................................57
9.1.2.4.
Physician’s Global Assessment of Disease Activity........................................57
9.1.2.5.
Safety of Estrogens in Lupus Erythematosus National 
Assessment (SELENA)-Systemic Lupus Erythematosus 
Disease Activity Index (SLEDAI) Flare Index................................................57
9.1.2.6.
Cutaneous Lupus Erythematosus Disease Area and 
Severity Index ................................................................................................58
9.1.2.7.
Lupus Low Disease Activity State..................................................................58
9.1.2.8.
Tender/Swollen Joint Count (28 Joints) ..........................................................58
9.1.2.9.
Systemic Lupus International Collaborating 
Clinics/American College of Rheumatology Damage 
Index ..............................................................................................................58
9.1.2.10.
British Isles Lupus Assessment Group Based Composite 
Lupus Assessment ..........................................................................................58
9.1.2.11.
Health Outcomes and Quality of Life Measures..............................................59
9.1.2.11.1.
Worst Pain Numeric Rating Scale.............................................................59
9.1.2.11.2.
Worst Joint Pain Numeric Rating Scale.....................................................59

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9.1.2.11.3.
Worst Fatigue Numeric Rating Scale ........................................................59
9.1.2.11.4.
Joint Stiffness Duration.............................................................................59
9.1.2.11.5.
Joint Stiffness Severity Numeric Rating Scale...........................................59
9.1.2.11.6.
Patient’s Global Impression of Severity ....................................................59
9.1.2.11.7.
Patient’s Global Impression of Change .....................................................60
9.1.2.11.8.
Medical Outcomes Short-Form 36-Item Health 
Survey Version 2 (SF-36v2) .....................................................................60
9.1.2.11.9.
Functional Assessment of Chronic Illness Therapy–
Fatigue Scale ............................................................................................60
9.1.2.11.10. Work Productivity and Activity Impairment 
Questionnaire–Lupus ................................................................................60
9.1.2.11.11. European Quality of Life–5 Dimensions–5 Levels ....................................60
9.1.3.
Appropriateness of Assessments ..........................................................................61
9.2.
Adverse Events ............................................................................................................61
9.2.1.
Serious Adverse Events........................................................................................62
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................63
9.2.2.
Adverse Events of Special Interest .......................................................................63
9.2.3.
Complaint Handling.............................................................................................63
9.3.
Treatment of Overdose.................................................................................................63
9.4.
Safety...........................................................................................................................63
9.4.1.
Electrocardiograms ..............................................................................................63
9.4.2.
Vital Signs ...........................................................................................................64
9.4.3.
Physical Examination...........................................................................................64
9.4.4.
Laboratory Tests ..................................................................................................64
9.4.5.
Columbia-Suicide Severity Rating Scale ..............................................................64
9.4.6.
16-Item Quick Inventory of Depressive Symptomatology:  
Self-Report...........................................................................................................65
9.4.7.
Chest x-Ray and Tuberculosis Testing..................................................................65
9.4.8.
Hepatitis B Virus  DNA Monitoring.....................................................................65
9.4.9.
Hepatic Safety Monitoring ...................................................................................66
9.4.10.
Safety Monitoring ................................................................................................67
9.4.10.1.
Venous Thromboembolic Event Assessment ..................................................67
9.5.
Pharmacokinetics .........................................................................................................67
9.6.
Pharmacodynamics ......................................................................................................69
9.7.
Pharmacogenomics ......................................................................................................69
9.7.1.
Whole Blood Samples for Pharmacogenetic Research..........................................69
9.8.
Biomarkers...................................................................................................................69
9.9.
Medical Resource Utilization and Health Economics ...................................................70
10.
Statistical Considerations ..................................................................................................71

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10.1. Sample Size Determination ..........................................................................................71
10.2. Populations for Analyses..............................................................................................72
10.3. Statistical Analyses ......................................................................................................72
10.3.1.
General Statistical Considerations ........................................................................72
10.3.1.1.
Analysis Methods...........................................................................................72
10.3.1.2.
Missing Data Imputation ................................................................................74
10.3.1.3.
Multiple Comparisons/Multiplicity.................................................................75
10.3.2.
Treatment Group Comparability...........................................................................78
10.3.2.1.
Patient Disposition..........................................................................................78
10.3.2.2.
Patient Characteristics ....................................................................................78
10.3.2.3.
Concomitant Therapy .....................................................................................78
10.3.2.4.
Treatment Compliance....................................................................................78
10.3.3.
Efficacy Analyses ................................................................................................78
10.3.3.1.
Primary Analyses ...........................................................................................78
10.3.3.2.
Major Secondary Analyses .............................................................................79
10.3.3.3.
Other Secondary and Exploratory Analyses ....................................................79
10.3.4.
Safety Analyses....................................................................................................79
10.3.4.1.
Adverse Events...............................................................................................79
10.3.4.2.
Clinical Laboratory Tests................................................................................80
10.3.4.3.
Vital Signs, Physical Findings, and Other Safety 
Evaluation ......................................................................................................80
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................80
10.3.6.
Interim Analyses..................................................................................................80
11.
References ........................................................................................................................82
12.
Appendices .......................................................................................................................86

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List of Tables
Table
Page
Table JAIA.1.
Schedule of Activities....................................................................................14
Table JAIA.2.
Objectives and Endpoints...............................................................................27
Table JAIA.3.
Treatment Regimens......................................................................................45
Table JAIA.4.
Criteria for Temporary Interruption of Investigational Product.......................52
Table JAIA.5.
Analysis Populations .....................................................................................72

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List of Figures
Figure
Page
Figure JAIA.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIA. ...................33
Figure JAIA.2.
Illustration of graphical multiple testing procedure with initial α 
allocation and weights. ..................................................................................77

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................87
Appendix 2.
Clinical Laboratory Tests...............................................................................92
Appendix 3.
Study Governance Considerations..................................................................94
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................99
Appendix 5.
Monitoring Tests for Confirmed VTE..........................................................100
Appendix 6.
Protocol Amendment I4V-MC-JAIA(b) Summary - A Randomized, 
Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of 
Baricitinib in Patients with Systemic Lupus Erythematosus .........................101

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1. Synopsis
Title of Study:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Study of Baricitinib 
in Patients with systemic lupus erythematosus (SLE).
Rationale:
Systemic lupus erythematosus is a chronic, often debilitating, multisystem, autoimmune disease 
that is characterized by the presence of autoreactive B cells and elevated autoantibodies, which 
directly damage the body’s cells and tissues.  Systemic lupus erythematosus can affect multiple 
organ systems simultaneously or sequentially, and follows a highly variable clinical course 
where periods of relatively stable disease are followed by flares and/or periods of persistently 
active disease; all of which can ultimately lead to irreversible damage to tissues and organ 
systems.
Baricitinib is an oral, reversible, selective inhibitor of Janus kinase (JAK)1 and JAK2 (Fridman 
et al. 2010).  This activity profile suggests that baricitinib may inhibit cytokines implicated in 
SLE, most notably type I interferon (IFN; JAK1/tyrosine kinase [TYK]2), interleukin (IL-6; 
JAK1/JAK2/TYK2), and type II IFNγ, as well as other cytokines that may have a role in SLE, 
including IL-23 (JAK2/TYK2), granulocyte–-macrophage colony stimulating factor 
(JAK2/JAK2) and IL-12 (JAK2/TYK2).  In a recently completed Phase 2 study (I4V-MC-JAHH 
[JAHH]), baricitinib demonstrated clinical efficacy in patients with SLE.  Baricitinib plus 
standard of care was superior to placebo plus standard of care in the proportion of patients 
achieving remission of rash and/or arthritis as defined by the Systemic Lupus Erythematosus 
Disease Activity Index 2000 (SLEDAI-2K), as well as the proportion of patients achieving a 
Systemic Lupus Erythematosus Responder Index-4 (SRI-4) response at Week 24. 
Given the efficacy of baricitinib demonstrated in clinical trials for treating 
autoimmune/autoinflammatory diseases involving joints, skin, and kidney (including SLE), the 
acceptable safety profile of baricitinib observed through the current stage of development, and a 
continuing unmet medical need in patients with SLE, there is a compelling rationale for the 
initiation of a Phase 3 program to evaluate baricitinib in treatment of SLE.

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Objective(s)/Endpoints:
Objectives
Endpoints
Primary
To evaluate the effect of baricitinib 4-mg QD and 
background standard-of-care (SoC) therapy compared 
with placebo and SoC on SLE disease activity.
Proportion of patients achieving an SRI-4 response at 
Week 52, defined as:

Reduction of ≥4 points from baseline in 
SLEDAI-2K score; and

No new British Isles Lupus Assessment Group 
(BILAG) A and no more than 1 new BILAG B 
disease activity score; and

No worsening (defined as an increase of ≥0.3 points 
[10 mm] from baseline) in the Physician’s Global 
Assessment of Disease Activity.
Major Secondary

To evaluate the effect of baricitinib 4-mg QD plus 
SoC compared to placebo plus SoC on SLE 
disease activity.

Proportion of patients achieving an SRI-4 response 
at Week 24.

Proportion of patients achieving a lupus low disease 
activity state (LLDAS) response at Week 52.

To evaluate the corticosteroid sparing effect of 
baricitinib 4-mg QD plus SoC compared to 
placebo plus SoC.

Proportion of patients receiving >7.5 mg prednisone 
(or equivalent) at baseline able to decrease dose by 
≥25% to a prednisone equivalent dose of ≤7.5 mg/day 
maintained between Week 40 and Week 52.

To evaluate the effect of baricitinib 4-mg QD plus 
SoC compared to placebo plus SoC on SLE flares.

Time to first severe flare over 52 weeks.

To evaluate the effect of baricitinib 4-mg QD plus 
SoC compared to placebo plus SoC on 
patient-reported outcomes (PROs).

Change from baseline in Worst Pain NRS at Week 
52.

Change from baseline in FACIT-Fatigue total score
at Week 52.

To evaluate the effect of baricitinib 2-mg QD plus 
SoC compared to placebo plus SoC on SLE 
disease activity.

Proportion of patients achieving an SRI-4 response
at Week 52.

Proportion of patients achieving an SRI-4 response 
at Week 24.

Proportion of patients achieving a lupus low disease 
activity state (LLDAS) response at Week 52.

To evaluate the corticosteroid sparing effect of 
baricitinib 2-mg QD plus SoC compared to 
placebo plus SoC.

Proportion of patients receiving >7.5 mg prednisone 
(or equivalent) at baseline able to decrease dose by 
≥25% to a prednisone equivalent dose of ≤7.5 mg/day 
maintained between Week 40 and Week 52.

To evaluate the effect of baricitinib 2-mg QD plus 
SoC compared to placebo plus SoC on SLE flares.

Time to first severe flare over 52 weeks.

To evaluate the effect of baricitinib 2-mg QD plus 
SoC compared to placebo plus SoC on 
patient-reported outcomes (PROs).

Change from baseline in Worst Pain NRS at Week 52.

Change from baseline in FACIT-Fatigue total score 
at Week 52
Abbreviations:  BILAG = British Isles Lupus Assessment Group; FACIT-Fatigue = Functional Assessment of 
Chronic Illness Therapy-Fatigue; LLDAS = Lupus Low Disease Activity State; NRS = Numeric Rating Scale; 
QD = once daily; SLE = Systemic Lupus Erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease 
Activity Index 2000; SoC = standard of care; SRI-4 = Systemic Lupus Erythematosus Responder Index-4.

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Summary of Study Design:
Study I4V-MC-JAIA (JAIA) is a Phase 3, multicenter, randomized, double-blind, parallel-group, 
placebo-controlled, outpatient, 52-week study evaluating the efficacy and safety of baricitinib 
4-mg and 2-mg in patients with SLE receiving standard therapy. Background standard therapies 
for SLE include corticosteroids, antimalarials, and immunosuppressants.
Treatment Arms and Duration:
At Week 0, patients will be randomized to 1 of 3 treatment groups: placebo once daily (QD), 
baricitinib 2-mg QD, or baricitinib 4-mg QD. The study duration will be up to 62 weeks 
(Screening Period: up to 6 weeks prior to randomization; Double-Blinded Treatment Period: 
52 weeks; [In some circumstances, due to COVID-19 related logistical issues, Visit 16 may be 
completed outside of the protocol specified timeframe, thus the treatment period may be 
extended.  Where allowed locally, additional IP (typically not to exceed 1 extra month’s supply) 
may be dispensed to prevent interruption of study drug.]; Follow-up Period: approximately 4 
weeks after the last dose of investigational product).
Number of Patients:
The study will include approximately 750 patients with SLE who will be randomized 1:1:1 to 
receive placebo QD, baricitinib 2-mg QD, or baricitinib 4-mg QD (250 patients in each treatment 
group). An additional 10% (75 patients) may be enrolled due to COVID-19 related trial impacts.
Statistical Analysis:
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the 
modified intent-to-treat (mITT) population, which includes randomized patients who receive at 
least 1 dose of investigational product.  Safety analyses will be conducted on those patients who 
receive at least 1 dose of investigational product who do not discontinue at the first postbaseline 
visit for the reason “Lost to Follow-up.”
Treatment comparisons of categorical efficacy and health outcomes variables will be made using 
a logistic regression analysis with Firth correction (Firth 1993; Heinze and Schemper 2001).  
Baseline disease activity, baseline corticosteroid dose, region, and treatment group will be 
explanatory variables in the model.  The p-value and 95% confidence interval (CI) for the odds 
ratio from the logistic regression model will be used for primary statistical inference.  Patients 
who discontinue treatment early, increased use of corticosteroids above the baseline dose other 
than the permitted burst, as defined in the SAP, or have initiation of or an increase above the 
baseline dose in immunosuppressant or antimalarial treatment any time after baseline, as defined 
in the SAP, will be defined as nonresponders and the data will be imputed using the 
nonresponder imputation (NRI) method.
Treatment comparisons of continuous efficacy and health outcomes variables will be made using 
a restricted maximum likelihood-based mixed model for repeated measures (MMRM) analysis.  
The model will include treatment, baseline disease activity, baseline corticosteroid dose, region, 

I4V-MC-JAIA(b) Clinical Protocol
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visit, treatment-by-visit interaction as fixed categorical effects, and baseline value and baseline 
value-by-visit interaction as fixed continuous effects to estimate change from baseline across 
postbaseline visits.  Type III tests for the least squares (LS) means will be used for the statistical 
comparisons.
Time to first flare will be analyzed using a Cox proportional hazards model with treatment 
group, baseline disease activity, baseline corticosteroid dose, and region fitted as explanatory 
variables.  Hazard ratios, 95% CI and p-values will be presented for treatment comparisons to 
placebo.
Missing data for patients who have COVID-19-related issues (that are not related to an adverse 
event of COVID-19 infection) may be imputed using alternative method, based on consultation 
with regulatory bodies, as appropriate.  Specific imputation methodologies, for this subgroup of 
patients, will be detailed in the SAP prior to the primary endpoint database lock.

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2. Schedule of Activities

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Table JAIA.1.
Schedule of Activities
Screening
Double-Blinded Treatment
Post-Treat
ment 
Follow-up
Visit Number
V1
V2a
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16b,c
ETd
V801e
Study Week
0
1
4
8
12
16
20
24
28
32
36
40
44
48
52
any
56 or last 
dose + 4 
weeks
Study Day
-42 to -3
1
8 ± 
3
29 ± 
4
57 ± 
4
85 ± 
4
113 
± 4
141 
± 4
169 
± 4
197 
± 4
225 
± 4
253 
± 4
281 
± 4
309 
± 4
337 
± 4
365 ± 
4
any
last dose + 
28  ± 5 
days
Procedures and Assessments
Informed consent
X
Demographics
X
Medical history
X
Physical examinationf
X
Symptom-directed 
physical examinationf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Waist circumference
X
X
X
X
X
X
Vital signs (BPg, 
pulse, temperature)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Substance use 
(caffeine, alcohol, 
tobacco)
X
ECGh
X
Administer TB testi
X
Read PPD test (if 
applicable)j
X
Chest x-rayk
X
Confirm SLE Criterial
X
Previous SLE therapy
X
X

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Screening
Double-Blinded Treatment
Post-Treat
ment 
Follow-up
Visit Number
V1
V2a
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16b,c
ETd
V801e
Study Week
0
1
4
8
12
16
20
24
28
32
36
40
44
48
52
any
56 or last 
dose + 4 
weeks
Study Day
-42 to -3
1
8 ± 
3
29 ± 
4
57 ± 
4
85 ± 
4
113 
± 4
141 
± 4
169 
± 4
197 
± 4
225 
± 4
253 
± 4
281 
± 4
309 
± 4
337 
± 4
365 ± 
4
any
last dose + 
28  ± 5 
days
Review 
inclusion/exclusion 
criteria 
X
X
Preexisting conditions
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C-SSRSm and
Self-Harm Supplement 
Form
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up 
Formn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16
X
X
X
X
X
X
X
X
Randomizationo
Xo
Log in IWRS
X
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigational product 
dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xc
Investigational product 
returned and 
compliance assessed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO (patient diary) 
dispensed/returnedp,q
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xp
Xp
Xp
Physician-Completed Scalesr
SLEDAI-2K
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BILAG-2004
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment of Disease 
Activity
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SLEDAI Flare Index
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAIA(b) Clinical Protocol
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Screening
Double-Blinded Treatment
Post-Treat
ment 
Follow-up
Visit Number
V1
V2a
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16b,c
ETd
V801e
Study Week
0
1
4
8
12
16
20
24
28
32
36
40
44
48
52
any
56 or last 
dose + 4 
weeks
Study Day
-42 to -3
1
8 ± 
3
29 ± 
4
57 ± 
4
85 ± 
4
113 
± 4
141 
± 4
169 
± 4
197 
± 4
225 
± 4
253 
± 4
281 
± 4
309 
± 4
337 
± 4
365 ± 
4
any
last dose + 
28  ± 5 
days
SLICC/ACR Damage 
Index
X
X
X
CLASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tender/swollen joint 
count (28 joints)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient Questionnaires
Worst Pain NRSq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Joint Pain NRSq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Fatigue NRSq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Joint Stiffness 
Durationq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Joint Stiffness Severity 
NRSq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Impression of Severity 
(PGI-S)q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Impression of Change 
(PGI-C)s
X
X
X
SF-36v2s
X
X
X
X
X
X
FACIT-Fatigues
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
WPAI-Lupuss
X
X
X
X
X
X
X
EQ-5D-5Ls
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
TSH
X
HIV
X

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Screening
Double-Blinded Treatment
Post-Treat
ment 
Follow-up
Visit Number
V1
V2a
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16b,c
ETd
V801e
Study Week
0
1
4
8
12
16
20
24
28
32
36
40
44
48
52
any
56 or last 
dose + 4 
weeks
Study Day
-42 to -3
1
8 ± 
3
29 ± 
4
57 ± 
4
85 ± 
4
113 
± 4
141 
± 4
169 
± 4
197 
± 4
225 
± 4
253 
± 4
281 
± 4
309 
± 4
337 
± 4
365 ± 
4
any
last dose + 
28  ± 5 
days
Hepatitis C virus 
(HCV) antibody 
testingt
X
Hepatitis B testing 
(HBsAg, HBcAb, 
HBsAb)
X
HBV DNAu
X
X
X
X
X
X
X
X
Serum pregnancy testv
X
Urine pregnancy testv
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
FSHw
X
Clinical chemistryx
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting lipid panely
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Iron studies (iron, 
TIBC, and ferritin)
X
X
X
X
X
Urinalysisz
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Creatinine and 
Protein, Ratio
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ANA
X
X
anti-dsDNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
anti-Smith
X
Autoantibodies 
(anti-Smith, anti-RNP, 
anti-SSA/Ro, 
anti-SSB/La)
X
X
X
X
X
Anti-cardiolipin 
antibodies IgG, IgA, 
IgM
X
X
X
X
X
X
X

I4V-MC-JAIA(b) Clinical Protocol
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Screening
Double-Blinded Treatment
Post-Treat
ment 
Follow-up
Visit Number
V1
V2a
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16b,c
ETd
V801e
Study Week
0
1
4
8
12
16
20
24
28
32
36
40
44
48
52
any
56 or last 
dose + 4 
weeks
Study Day
-42 to -3
1
8 ± 
3
29 ± 
4
57 ± 
4
85 ± 
4
113 
± 4
141 
± 4
169 
± 4
197 
± 4
225 
± 4
253 
± 4
281 
± 4
309 
± 4
337 
± 4
365 ± 
4
any
last dose + 
28  ± 5 
days
Anti-beta-2 
glycoprotein-I (IgG, 
IgM)
X
X
X
X
X
X
X
Lupus anticoagulant 
(dRVVT)
X
X
X
X
X
X
X
Complement (C3 and 
C4)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunoglobulins 
(IgG, IgA, IgM)
X
X
X
X
X
X
X
X
Lymphocyte subsets 
(T, B, NK, and T cell 
subsets)
X
X
X
X
X
X
X
X
Exploratory storage 
samples (serum and 
plasma)
X
X
X
X
X
Exploratory storage 
samples (urine)
X
X
X
X
X
Exploratory samples 
for storage (RNA)
X
X
X
X
X
Baricitinib plasma 
concentrations (PK 
sample)
Xaa
Xaa
Xaa
Xaa
Xaa
Xaa
Pharmacogenetic 
(DNA) collectionbb
X
X
X

I4V-MC-JAIA(b) Clinical Protocol
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Abbreviations:  ANA = antinuclear antibody; BILAG = British Isles Lupus Assessment Group; BP = blood pressure; CLASI = Cutaneous Lupus Erythematosus 
Disease Area and Severity Index; COVID-19 = coronavirus disease; C-SSRS = Columbia-Suicide Severity Rating Scale; dRVVT = Dilute Russell’s Viper 
Venom Time; dsDNA = double-stranded deoxyribonucleic acid; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; ePRO = electronic 
patient-reported outcomes; EQ-5D = EuroQol-5Dimensions; ET = early termination; FACIT-Fatigue = Functional Assessment of Chronic Illness 
Therapy-Fatigue; FSH = follicle‑stimulating hormone; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B 
surface antigen; HBV DNA = hepatitis B virus deoxyribonucleic acid; HIV = human immunodeficiency virus; Ig = immunoglobulins; IWRS = interactive 
web-response system; NRS = Numerical Rating Scale; PK = pharmacokinetics; PGI-C = Patient’s Global Impression of Change; PPD = purified protein 
derivative; QIDS-SR16 = Quick Inventory of Depressive Symptomatology; RNA = ribonucleic acid; RNP = ribonucleoprotein; SF-36 = Short-Form 36-item 
Health Survey; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC/ACR = Systemic 
Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology; SSA/Ro = Sjögren’s-Syndrome-related antigen A; 
SSB/La = Sjögren syndrome type B antigen/Lupus La protein; TB = tuberculosis; TIBC = total iron binding capacity; TSH = thyroid-stimulating hormone; 
V = visit; WPAI-Lupus = Work Productivity and Activity Impairment-Lupus.
a
At Visit 2, all baseline assessments must be performed and baseline laboratory samples must be drawn PRIOR to administration of the first dose of 
investigational product for randomized patients.
b Patients who complete the treatment period through Visit 16 may be eligible to participate in the long-term extension study (I4V-MC-JAIM [JAIM]).  For 
patients enrolled in JAIM, Visit 1 of Study JAIM should occur on the same day as Visit 16 of Study I4V-MC-JAIA (JAIA).  In some circumstances, due to 
COVID-19 related logistical issues, patients who were unable to complete Visit 16 in the protocol specified timeframe and had study drug temporarily 
interrupted, but otherwise completed the treatment period, may be eligible to participate in Study JAIM.
c
In some circumstances, due to COVID-19 related logistical issues, Visit 16 may be completed outside of the protocol specified timeframe. Where allowed 
locally, additional investigational product (IP, typically not to exceed 1 extra month’s supply) may be dispensed to prevent interruption of study drug during 
the treatment period.
d Those patients who discontinue from the study prior to Visit 16 should complete the ET visit and proceed to post-treatment follow-up.
e
Patients should return for Visit 801, a post-treatment follow-up visit, 28±5 days after the last dose of investigational product.  Patients who complete the 
treatment period through Visit 16 and enter the long-term extension (LTE; JAIM) will not complete Visit 801 in Study JAIA, as they will complete 
post-treatment follow-up at the conclusion of JAIM. Patients who discontinue IP but remain in the study for at least 28±5 days without IP can combine their 
Visit 16/ET with their Visit 801 (post-treatment follow-up visit).
f
One complete physical examination (excluding pelvic and rectal examinations) will be performed at Visit 1.  All subsequent physical examinations may be 
symptom-directed.  A complete physical examination may be repeated at the investigator’s discretion any time.
g At each time point, 3 replicate readings should be made at approximately 30- to 60-second intervals.  Blood pressure is recorded as the average of these three 
readings.  A single pulse measurement should be made simultaneously with at least one of the readings at each time point (Section 9.4.2.  Vital Signs).
h 12-lead ECGs (single) will be performed locally and will be locally (machine) read.

I4V-MC-JAIA(b) Clinical Protocol
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i
TB test(s) include PPD, QuantiFERON®-TB Gold, and T SPOT®.  See Exclusion Criterion [29] for details of TB testing.  In countries where the 
QuantiFERON-TB Gold test or T-SPOT is available, either test may be used instead of the PPD TB test.  The QuantiFERON-TB Gold test must be performed 
centrally; the T-SPOT must be performed locally.  Note:  Exception:  Patients with a history of active or latent TB who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was completed, have no clinical features of active TB, and have a screening chest 
x-ray with no evidence of active TB are not required to undergo the protocol-specific TB testing (i.e., PPD, QuantiFERON®-TB Gold, or T SPOT®) but must 
have a chest x-ray at screening (i.e:  chest imaging performed within the past 6 months will not be accepted).
j
For those patients with a PPD placed at Visit 1, the PPD must be read 2 to 3 days (48 to 72 hours) post-Visit 1.  Purified protein derivative does not need to be 
read at the site, but must be read by a trained medical professional and results must be presented to the site at Visit 2.
k A chest x-ray (posterior-anterior view) will be performed at screening unless chest imaging (excluding ultrasound) has been performed within the past 6 
months and the imaging and reports are available for review by the investigator.
l
Prior to randomization, there must be documentation of a patient having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus 
Erythematosus according to the 1997 Update of the 1982 ACR criteria for classification of SLE (Tan et al. 1982; Hochberg et al. 1997).  See Inclusion 
Criterion [3].
m Suicidal ideation and behavior subscales excerpt; adapted for the assessment of 11 preferred ideation and behavior categories.  C-SSRS and Self-Harm 
Supplement Form should be completed after collection of unsolicited adverse events.
n The Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form.
o Patient eligibility must be reviewed and confirmed by an eligibility review committee prior to randomization.  At Visit 2, patients will be randomized with 
stratification in IWRS, by total SLEDAI-2K score from Screening, corticosteroid dose at baseline, and region.  The Screening eGFR result must also be 
entered into IWRS for appropriate dose adjustment to occur if necessary.
p ePRO devices (daily patient diaries) should be dispensed to all patients at screening and will need to be collected from screen-failed patients.  Patients are 
encouraged to bring the ePRO device to every visit; however, if they do not bring the device, this will not be a protocol deviation.  For patients NOT entering 
the LTE, the patient diary will be returned at Visit 801 or the patient’s last visit.  For patients entering the LTE, the patient diary will be returned at Visit 16.
q Worst Pain NRS, Worst Joint Pain NRS, Worst Fatigue NRS, Joint Stiffness Duration, Joint Stiffness Severity NRS, and PGI-S will be collected on an 
electronic patient diary daily (ePRO device) starting at Visit 1 (screening) through Visit 16 (or Visit 801 for those not entering the LTE Study JAIM) and 
should be completed prior to any clinical assessments on days when study visits occur.
r
SLE assessments must be completed by a physician and will be documented on an eCOA (electronic clinical outcome assessment) device.
s
Patient-reported questionnaires will be administered via an on-site eCOA device and should be administered prior to any clinical assessments.
t
For patients who are positive for HCV antibody, a follow-up test for HCV RNA will be performed automatically.  Patients who are positive for HCV antibody 
and negative for HCV RNA may be enrolled.
u For patients who are positive for HBcAb, a follow-up test for HBV DNA will be performed automatically.  Patients who are positive for HBcAb and negative 
for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive, regardless of HBsAb status or level, must undergo HBV DNA testing per the 
schedule of events (see Section 9.4.8 for details of HBV DNA monitoring).
v For all women of child-bearing potential, a serum pregnancy test (central laboratory) will be performed at Visit 1.  Urine pregnancy tests (local laboratory) 
will be performed at Visit 2 prior to randomization and at all subsequent study visits.

I4V-MC-JAIA(b) Clinical Protocol
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w For female patients ≥50 and <55 years of age who have had a cessation of menses for at least 6 and less than 12 months, an FSH test will be performed to 
confirm non-child-bearing potential (FSH ≥40 mIU/mL).
x Clinical chemistry will include the following value calculated by the central laboratory from serum creatinine: estimated glomerular filtration rate (eGFR; 
calculated using the Modification of Diet in Renal Disease [MDRD] isotope dilution mass spectrometry traceable method).
y Fasting lipid profile. Patients should not eat or drink anything except water for 12 hours prior to sample collection.  If a patient attends these visits in a 
nonfasting state, the sample should still be collected.  This will not be considered a protocol violation.
z
Urine should be collected as a clean catch sample.
aa See Section 9.5 for details.
bb Patients choosing not to provide consent for whole blood samples to be collected for pharmacogenetic research will still be eligible to participate in the study.

I4V-MC-JAIA(b) Clinical Protocol
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3. Introduction
3.1.
Study Rationale
Baricitinib is an oral, reversible, selective inhibitor of Janus kinase (JAK)1 and JAK2 (Fridman 
et al. 2010).  This activity profile suggests that baricitinib may inhibit cytokines implicated in 
systemic lupus erythematosus (SLE), most notably type I interferon (IFN JAK1/TYK2), 
interleukin (IL)-6 (JAK1/JAK2/TYK2), and type II IFN-, as well as other cytokines that may 
have a role in SLE, including IL-23 (JAK2/TYK2), granulocyte-macrophage colony stimulating 
factor (JAK2/JAK2) and IL-12 (JAK2/TYK2).  The potential impact of baricitinib on the IFN 
pathway is relevant to SLE, as clinical and preclinical studies have established that this pathway 
is involved in the pathogenesis of SLE (Hoffman et al. 2017).  Suppressing the IFN signature 
through the use of a monoclonal antibody that targets the type I IFN receptor has been shown to 
be effective in SLE (Furie et al. 2017).  Baseline gene expression in SLE, examined as part of the 
ILLUMINATE Phase 3 trials, demonstrated upregulation of IL–6-related genes, IL-2 receptor, 
IL-12, and oncostatin M in patients with SLE compared to control subjects, all of which signal 
through the JAK/signal transducers and activators of transcription (STAT) pathways and would 
not be anticipated to be directly modulated by therapeutic strategies which only target the IFN 
pathway (Hoffman et al. 2017).  Thus, baricitinib is anticipated to be effective as it modulates 
not only IFN but also other potential SLE-relevant pathways, providing a biologic rationale for 
its evaluation in this disease.
Baricitinib has demonstrated clinical efficacy and safety in patients with autoimmune (SLE, 
rheumatoid arthritis [RA; Taylor et al. 2015; Fleischmann et al. 2016; Genovese et al. 2016; 
Dougados et al. 2017]) and autoinflammatory diseases (Chronic atypical neutrophilic dermatosis 
with lipodystrophy and elevated temperature [CANDLE], Stimulator of Interferon Genes 
(STING)-Associated Vasculopathy With Onset During Infancy [SAVI], Juvenile 
Dermatomyositis [JDM], and Aicardi-Goutières Syndrome [AGS]) (Montealegre Sanchez et al. 
2018). A Phase 2 study of baricitinib in patients with SLE demonstrated that baricitinib 4-mg 
plus standard of care (SoC) was superior to placebo plus SoC in the proportion of patients 
achieving remission of rash and/or arthritis as defined by the Systemic Lupus Erythematosus 
Disease Activity Index 2000 (SLEDAI-2K) at Week 24 (67.3% baricitinib 4-mg, 58.1% 
baricitinib 2-mg, 53.3% placebo, p<0.05 for baricitinib 4-mg versus placebo).  Patients treated 
with baricitinib 4-mg also had a higher Systemic Lupus Erythematosus Responder Index-4 
(SRI-4) response rate at Week 24 compared to patients treated with placebo (64.4% baricitinib 
4-mg, 51.4% baricitinib 2-mg, 47.6% placebo, p<0.05 for baricitinib 4-mg versus placebo) (Eli 
Lilly and Company data on file, 2017).  Additionally, completed Phase 2 studies of baricitinib 
also demonstrated efficacy in patients with moderate-to-severe plaque psoriasis (Papp et al. 
2016), diabetic kidney disease (Tuttle et al. 2015), and atopic dermatitis (Guttman-Yassky et al. 
2018).
Given the efficacy of baricitinib demonstrated in clinical trials for treating 
autoimmune/autoinflammatory diseases involving joints, skin, and kidney (including SLE), the 
acceptable safety profile of baricitinib observed through the current stage of development, and a 

I4V-MC-JAIA(b) Clinical Protocol
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continuing unmet medical need in patients with SLE, there is a compelling rationale for initiation 
of a Phase 3 program to evaluate baricitinib in the treatment of SLE.
3.2.
Background
Systemic lupus erythematosus is a chronic, often debilitating, multisystem, autoimmune disease 
that is characterized by the presence of autoreactive B cells and elevated autoantibodies, which 
directly damage the body’s cells and tissues.  Systemic lupus erythematosus can affect multiple 
organ systems simultaneously or sequentially, and follows a highly variable clinical course 
where periods of relatively stable disease are followed by flares and/or periods of persistently 
active disease; all of which can ultimately lead to irreversible damage to tissues and organ 
systems.
Systemic lupus erythematosus is predominately a disease of women (approximately 9:1 female 
to male ratio), which can begin at any age but most commonly begins in adolescence or early 
adulthood (Yu et al. 2017).  It affects 20 to 150 in 1,000,000 people in the US (UpToDate® 2018 
[WWW]) and is more common in African-Americans (Lim et al. 2014; Somers et al. 2014), with 
as many as 1 in 537 African-American women afflicted with SLE (Somers et al. 2014).  
Additionally, SLE appears to be more severe in African-Americans, Asian-Americans, and 
Latinos compared to Caucasians (Kaslow 1982; Alarcón et al. 2001).
Clinically, SLE presents with varying signs and symptoms, including fever, arthralgia/arthritis, 
skin rash, alopecia, pleuritis, pericarditis, nephritis, vasculitis, stroke, seizure, leukopenia, 
thrombocytopenia, anemia, photosensitivity, and the presence of autoantibodies reactive with 
nuclear antigens.  Fatigue is the most prevalent symptom reported among patients with SLE 
(Avina-Zubieta et al. 2007).  Pain that interferes with daily living activities is also commonly 
reported (Ozel and Argon 2015).  Skin and joint disease are also among the most prevalent 
features of the illness.  Age, USA African race/ethnicity, SLEDAI-2K score, steroid use, and 
hypertension were associated with transition from no damage to damage, and increase(s) in 
preexisting damage (Bruce et al. 2015).  Over 60% of patients with SLE will develop clinically 
detectable organ damage within 2 to 7 years of diagnosis, as measured by the Systemic Lupus 
Erythematosus International Collaborating Clinics (SLICC)/American College of Rheumatology
(ACR) damage index (Cooper et al. 2007).
Improvements in earlier diagnosis, treatment regimens, and medical care over the past several 
decades have reduced mortality in SLE.  However, patients continue to experience premature 
death, with cardiovascular disease being the leading cause.  A recent meta-analysis of published 
data involving over 27,000 patients with SLE observed a 3-fold increase in the risk of death in 
patients with SLE compared with the general population (Yurkovich et al. 2014).  Morbidity 
remains substantial as measured by various tools for features such as health-related quality of 
life, loss of work productivity, pain, and fatigue (Avina-Zubieta et al. 2007; Ozel and Argon 
2015).  Thus, there remains substantial unmet medical need for individuals who have SLE.
Standard of care (SoC) for SLE includes antimalarial agents, corticosteroids, nonsteroidal 
anti-inflammatory drugs (NSAIDs), immunosuppressive agents, and cytotoxic agents; however, 
there are relatively few drugs approved for the treatment of SLE.  For example, in the US, 

I4V-MC-JAIA(b) Clinical Protocol
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approved therapies for SLE include aspirin, antimalarials, corticosteroids, and belimumab.  In 
general, treatment regimens are broadly similar around the world and are tailored to the severity 
of disease and the specific organs involved.  Mild disease is often treated with low-dose 
corticosteroids, NSAIDs, and antimalarials; while serious, organ-threatening or life-threatening 
disease is typically treated with high-dose corticosteroids and immunosuppressive agents.  In 
addition to their direct impact on disease, immunosuppressive agents are also utilized as so 
called “corticosteroid-sparing agents” to reduce chronic exposure to corticosteroids.
The current SoC therapies have broad effects on immune and inflammatory pathways, including 
host defense, and have been associated with short- and long-term morbidity.  For example, 
long-term use of corticosteroids is associated with cataracts, osteoporosis, avascular necrosis, 
increased infection, cardiovascular events, hyperglycemia, and weight gain, while 
cyclophosphamide increases the risk of premature ovarian failure, serious infection, and cancer.
Although recent improvements in treatment regimens and medical care have reduced overall 
morbidity and mortality, many patients still have incompletely controlled disease and progress to 
end-stage organ involvement.  In addition, the disease increases mortality and negatively impacts 
health-related quality of life.  New treatment options with an acceptable safety profile that reduce 
disease activity, reduce flares, delay organ damage, and reduce the requirement for 
corticosteroids and cytotoxic agents are urgently needed for patients with SLE.
Accordingly, pharmacologic interventions that target specific pathways associated with the 
pathology of SLE may provide novel therapeutic approaches to disease management.  One of the 
signaling pathways implicated in SLE disease activity is the type I IFN signaling pathway.  
Upregulation of genes associated with the activation of type I IFN signaling, referred to as a type 
I IFN signature, is observed in approximately 75% of patients with SLE (Hoffman et al. 2017).  
In SLE, a high type I IFN signature was associated with increased disease severity as measured 
by SLEDAI score, increased anti–double-stranded deoxyribonucleic acid (anti-dsDNA), 
decreased complement, and increased risk of severe flares (Hoffman et al. 2017).  Another 
cytokine implicated in the pathogenesis of SLE is IL-6.  Increased expression of IL-6 has been 
found in murine models of SLE and in patients with SLE, and inhibition of IL-6 signaling was 
associated with a decrease in disease activity (Linker-Israeli et al. 1999, Illei et al. 2010).  Both 
type I IFNs and IL-6 signal through the JAK/STAT pathway; therefore, treatment of SLE with 
baricitinib or other JAK inhibitors is an area of intense interest.
3.3.
Benefit/Risk Assessment
Phase 2 SLE Data
In the baricitinib Phase 2 SLE clinical Study I4V-MC-JAHH (JAHH), significant benefit for 
baricitinib 4-mg once daily (QD) treatment over placebo was demonstrated for the primary 
efficacy endpoint of resolution of arthritis and/or rash, the major secondary efficacy endpoint of 
SRI-4 response, and important supporting measures such as flare and lupus low disease activity 
score (LLDAS) after 24 weeks of treatment.  Baricitinib 2-mg QD was numerically better than 
placebo across these measures although the results were not statistically significant.

I4V-MC-JAIA(b) Clinical Protocol
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The percentage of patients with at least 1 treatment-emergent adverse event (TEAE) during the 
24-week treatment period was 64.8% for placebo, 71.4% for baricitinib 2-mg QD, and 73.1% for 
baricitinib 4-mg QD.  The most common TEAEs (occurring in ≥5% of patients in either 
baricitinib dose group over 24 weeks) were viral upper respiratory tract infection, urinary tract 
infection, upper respiratory tract infection, pharyngitis, and headache.  The proportions of 
patients who reported viral upper respiratory tract infections were higher for baricitinib-treated 
patients compared to placebo, but the proportions were similar for the baricitinib 2-mg and 4-mg 
dose groups. It is important to consider that in SLE, patients are at an increased risk for 
infections due to predisposing conditions related to impaired cellular and humoral immune 
functions (Danza and Ruiz Irastorza 2013), as well as concomitant use of immunosuppressive 
agents such as corticosteroids.  In the Phase 2 study of baricitinib, there were more serious 
infections reported in the baricitinib 4-mg group versus the baricitinib 2-mg group or placebo.  
There were no cases of serious herpes zoster or opportunistic infection, and no reports of 
tuberculosis (TB).  There were no malignancies or major adverse cardiovascular events (MACE) 
reported.  One serious adverse event (SAE) of deep vein thrombosis (DVT) was reported in the 
baricitinib 4-mg group, in a patient with pre-existing antiphospholipid antibodies and pain in the 
affected limb (right calf) prior to study entry, who was taking a concomitant oral corticosteroid 
and celecoxib during the study.  
Risks Identified in the Baricitinib Program
Serious infections, venous thromboembolism, hepatotoxicity, and fetal malformations were 
identified as important potential risks with baricitinib. Inclusion/Exclusion criteria in the 
protocol limit enrolment of SLE patients who are at risk for these important potential risks.  
Although infections were seen in about half of the SLE study population, the incidence rate of 
serious infection in patients exposed to baricitinib in the RA program was only 3.0 per 100 
patient-years.  During the controlled period (through 16 weeks), rates were similar in both 
baricitinib- and placebo-treated patients. The nonserious infections (upper respiratory tract 
infections, herpes zoster, and herpes simplex) associated with baricitinib in the RA program are 
readily diagnosed, manageable, and typically resolve without long-term sequelae.  It is 
recommended that where indicated, herpes zoster vaccination be offered to patients prior to 
receiving baricitinib.
Increases in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and 
total bilirubin have been seen in patients with RA. Most of these increases improved with 
continued use or temporary discontinuation of baricitinib with no long-term effects. No cases of 
severe drug-induced liver injury were observed with baricitinib treatment.
Fetal malformations were reported in toxicology studies at higher doses than what is used in 
human patients.  Only a small number of patients have become pregnant in baricitinib clinical 
trials, and there have been no reports of fetal malformations in these pregnancies. 
Venous thromboembolic events (VTEs) have been determined to be an important potential risk 
for baricitinib.  There was a numerical imbalance in reports of VTEs in the 24-week 
placebo-controlled period of the Phase 3 trials of patients with RA.  Available evidence does not 

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establish a causal association.  With long-term exposures, the exposure-adjusted incidence rate of 
VTE for baricitinib-treated patients with RA was similar to the background rates published in the 
literature for the target population.  There was no pattern of increased or decreased risk during 
long-term exposures, and cases observed with baricitinib were confounded by one or more 
recognized risk factors for VTE.  Venous thromboembolic event risk can be managed through 
risk mitigation strategies.  Exclusion and discontinuation criteria have been added to the protocol 
to limit participation of patients who are at an increased risk of VTE.
Therefore, in the context of the cumulative knowledge, the benefit/risk balance for baricitinib in 
the treatment of adult patients with SLE is assessed to be favorable.
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated adverse events (AEs) of baricitinib are to be found in the Investigator’s Brochure 
(IB).

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4.
Objectives and Endpoints
Table JAIA.2 shows the objectives and endpoints of the study.
Table JAIA.2.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the effect of baricitinib 4-mg QD and 
background standard-of-care (SoC) therapy compared 
to placebo and SoC on SLE disease activity.
Proportion of patients achieving an SRI-4 response at 
Week 52, defined as:

Reduction of ≥4 points from baseline in 
SLEDAI-2K score; and

No new British Isles Lupus Assessment Group 
(BILAG) A and no more than 1 new BILAG B 
disease activity score; and

No worsening (defined as an increase of 
≥0.3 points [10 mm] from baseline) in the 
Physician’s Global Assessment of Disease 
Activity.
Major Secondary (Multiplicity Controlled)

To evaluate the effect of baricitinib 4-mg QD plus 
SoC compared to placebo plus SoC on SLE 
disease activity.

Proportion of patients achieving an SRI-4 response 
at Week 24.

Proportion of patients achieving a lupus low 
disease activity state (LLDAS) response at Week 
52

To evaluate the corticosteroid sparing effect of 
baricitinib 4-mg QD plus SoC compared to 
placebo plus SoC.

Proportion of patients receiving >7.5 mg 
prednisone (or equivalent) at baseline able to 
decrease dose by ≥25% to a prednisone equivalent 
dose of ≤7.5 mg/day maintained between Week 40 
and Week 52.

To evaluate the effect of baricitinib 4-mg QD plus 
SoC compared to placebo plus SoC on SLE flares.

Time to first severe flare over 52 weeks.

To evaluate the effect of baricitinib 4-mg QD plus 
SoC compared to placebo plus SoC on 
patient-reported outcomes (PROs).

Change from baseline in Worst Pain NRS at Week 
52.

Change from baseline in FACIT-Fatigue total 
score at Week 52.

To evaluate the effect of baricitinib 2-mg QD plus 
SoC compared to placebo plus SoC on SLE 
disease activity.

Proportion of patients achieving an SRI-4 response
at Week 52.

Proportion of patients achieving an SRI-4 response 
at Week 24.

Proportion of patients achieving a lupus low 
disease activity state (LLDAS) response at Week 
52

To evaluate the corticosteroid sparing effect of 
baricitinib 2-mg QD plus SoC compared to 
placebo plus SoC.

Proportion of patients receiving >7.5 mg 
prednisone (or equivalent) at baseline able to 
decrease dose by ≥25% to a prednisone equivalent 
dose of ≤7.5 mg/day maintained between Week 40 
and Week 52.

To evaluate the effect of baricitinib 2-mg QD plus 

Time to first severe flare over 52 weeks.

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SoC compared to placebo plus SoC on SLE flares.

To evaluate the effect of baricitinib 2-mg QD plus 
SoC compared to placebo plus SoC on 
patient-reported outcomes (PROs).

Change from baseline in Worst Pain NRS at Week 
52.

Change from baseline in FACIT-Fatigue total 
score at Week 52
Other Secondary (Non-Multiplicity Controlled)
[1] To evaluate the effect of baricitinib 4-mg or 2-mg 
QD plus SoC compared to placebo plus SoC on 
SLE disease activity.

Change from baseline in total SLEDAI-2K scores
over time through Week 52.

Change from baseline in PGA score over time 
through Week 52.

Proportion of patients achieving an SRI-4 response 
over time through Week 52.

Proportion of patients achieving an SRI-5, -6, -7, 
and -8 response over time through Week 52.

Proportion of patients achieving reduction of ≥4 
points from baseline in SLEDAI-2K score at Week 
52.

Proportion of patients with no new British Isles 
Lupus Assessment Group (BILAG) A and no more 
than 1 new BILAG B disease activity score at 
Week 52.

Proportion of patients with no worsening (defined 
as an increase of ≥0.3 points [10 mm] from 
baseline) in the Physician’s Global Assessment of 
Disease Activity at Week 52.

Proportion of patients achieving a British Isles 
Lupus Assessment Group Based Composite Lupus 
Assessment (BICLA) response at Week 52, 
defined as: 
Reduction of all baseline BILAG A to B/C/D 
and baseline BILAG B to C/D, and no BILAG 
worsening in other organ systems, where 
worsening is defined as ≥1 new BILAG A or ≥2 
new BILAG B
No worsening from baseline in SLEDAI-2K, 
where worsening is defined as an increase from 
baseline of >0 points in SLEDAI-2K

No worsening from baseline in participants' 
lupus disease activity, where worsening is 
defined by an increase ≥0.30 points on a 3-point 
PGA visual analogue scale (VAS).
[2] To evaluate the corticosteroid sparing effect of 
baricitinib 4-mg or 2-mg QD plus SoC compared 
to placebo plus SoC.

Change from baseline in prednisone dose at 
Week 52.

Proportion of patients taking corticosteroids at 
baseline able to discontinue use at Week 52.
[3] To evaluate the effect of baricitinib 4-mg or 2-mg 
QD plus SoC compared to placebo plus SoC on 
SLE flares.

Time to first mild/moderate flare over 52 weeks.

Time to first flare (any severity) over 52 weeks.

Annualized mild/moderate flare rate

Annualized severe flare rate

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
Annualized flare rate (any severity)
[4] To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC 
on mucocutaneous manifestations of SLE.

Proportion of patients with CLASI total activity 
score ≥ 10 at baseline with ≥50% reduction in 
CLASI total activity score at Week 52.

To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC 
on musculoskeletal manifestations of SLE.

Change from baseline in tender joint count at 
Week 52.

Change from baseline in swollen joint count at 
Week 52.

To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC 
on individual organ system disease activity.

Proportion of patients with improvement in each 
SLEDAI-2K organ system versus baseline at Week 
52.

Proportion of patients with worsening in each 
SLEDAI-2K organ system versus baseline at Week 
52.

To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC
on PROs.

Change from baseline in Worst Fatigue NRS at 
Week 52.

Change from baseline in Worst Joint Pain NRS at 
Week 52.

Change from baseline in Joint Stiffness Duration at 
Week 52.

Change from baseline in Joint Stiffness Severity 
NRS at Week 52.

Change from baseline in Patient Global Impression 
of Severity at Week 52. 

Change from baseline in Patient Global Impression 
of Change at Week 52

Change from baseline in mental component score 
(MCS), physical component score (PCS), and 
domain scores in the Short-Form 36-item health 
survey version 2 (SF-36v2) acute at Week 52.

Change from baseline in the EQ-5D-5L at 
Week 52.

Change from baseline in the WPAI-Lupus at Week 
52.

To measure baricitinib PK exposure and assess the 
relationship between exposure and efficacy.

Population pharmacokinetics of baricitinib in 
patients with SLE.

Proportions of patients achieving SRI-4 by 
exposure quartile.
Exploratory

To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC 
on damage.

Change from baseline in SLICC/ACR damage 
index total score at Week 52.

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
To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC 
on serologic markers of SLE.

Change from baseline in IFN signature over 52 
weeks.

Change from baseline in anti-dsDNA level in 
patients with elevated anti-dsDNA at baseline over 
52 weeks.

Change from baseline in C3 and/or C4 levels in 
patients with low C3 and/or C4 at baseline over 52 
weeks.

To evaluate the effect of baricitinib 4-mg QD or 
2-mg QD plus SoC compared to placebo plus SoC 
on SLE disease activity in subgroups of interest.

Proportion of patients with high IFN signature 
achieving an SRI-4 response at Week 52.
Abbreviations:  ACR = American College of Rheumatology; BILAG = British Isles Lupus Assessment Group; 
C3 = complement 3; C4 = complement 4; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity 
Index; dsDNA = double-stranded deoxyribonucleic acid; EQ-5D-5L = European Quality of Life–5 Dimensions–
5 Levels; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy–Fatigue Scale; IFN = interferon; 
MCS = Mental Component Score; NRS = Numeric Rating Scale; PCS = physical component score; 
PGA = Physician Global Assessment; PK = pharmacokinetic; QD = once daily; SF-36v2 = Short-Form 36-item 
health survey version 2; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus 
Disease Activity Index 2000; SLICC = Systemic Lupus Erythematosus International Collaborating Clinics; 
SoC = standard of care; SRI = Systemic Lupus Erythematosus Responder Index; WPAI-Lupus = Work 
Productivity and Activity Impairment Questionnaire-Lupus.

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5. Study Design
5.1.
Overall Design
Study I4V-MC-JAIA (JAIA) is a Phase 3, multicenter, randomized, double-blind, parallel-group, 
placebo-controlled, outpatient, 52-week study evaluating the efficacy and safety of baricitinib 
4-mg and 2-mg in patients with SLE receiving standard therapy.
Approximately 750 patients will be randomized at a 1:1:1 ratio to receive baricitinib 4-mg daily, 
baricitinib 2-mg daily, or placebo (250 patients per treatment group).  Patients will be stratified 
at randomization according to disease activity (total SLEDAI-2K at screening <10; ≥10), 
corticosteroid dose at baseline (<10 mg/day; ≥10 mg/day prednisone or equivalent), and region 
(defined in the statistical analysis plan [SAP]).
All procedures to be conducted during the study, including timing of all procedures, are indicated 
in the Schedule of Activities (Section 2).  Section 7.7 describes permitted concomitant therapy.  
Study governance considerations are described in detail in Appendix 3.
Figure JAIA.1 illustrates the study design.
The study consists of 3 periods:
Screening Period:  The screening period is up to 42 days and begins when the patient signs the 
informed consent form (ICF).  In exceptional circumstances, the screening window can be 
extended after consultation with the sponsor.  During the screening period, the site must confirm 
the patient meets all inclusion and no exclusion criteria for the study (see Section 6).  Screening 
procedures will be performed according to the Schedule of Activities (Section 2).  Patient 
eligibility will be reviewed and confirmed by an eligibility review committee prior to 
randomization.  Eligible patients will be randomized at Week 0 (Visit 2).
Treatment Period:
At Visit 2 (Week 0, baseline) after all assessments are completed and baseline laboratory 
samples obtained according to the Schedule of Activities, randomized patients will take the first 
dose of investigational product at the clinic and pharmacokinetic (PK) samples will be drawn 15 
minutes and 1 hour postdose.  
Investigational product will be taken daily for 52 weeks. In some circumstances, due to 
COVID-19 related logistical issues, Visit 16 may be completed outside of the protocol specified 
timeframe, thus the treatment period may be extended.  Where allowed locally, additional IP 
(typically not to exceed 1 extra month’s supply) may be dispensed to prevent interruption of 
study drug.  Clinical assessments and laboratory samples, including additional PK sampling, will 
be obtained at scheduled visits according to the Schedule of Activities (Section 2).  Special 
timing considerations of administration of investigational product relative to PK sample 
collection at study visits are described in Section 9.5.
During the treatment period, in addition to randomized treatment, patients will also maintain 
their usual medication regimen for SLE, including background standard-of-care therapy 

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consisting of corticosteroids, antimalarials, and/or immunosuppressants (see Section 6.1, 
Inclusion Criterion [8] and Section 7.7 for details).
Between Weeks 0 through 12 of the treatment period, patients with intolerable disease activity 
may receive a single corticosteroid burst if necessary.  See Section 7.7.1 for details.
Between Weeks 0 through 16 and Weeks 24 through 40 of the treatment period, investigators are 
encouraged to taper corticosteroids according to clinical practice, with a goal of ≤7.5 mg/day
prednisone (or equivalent) by Week 40 (Visit 13).  In most cases, tapering should not be 
considered for at least 4 weeks after randomization, consistent with clinical practice.  If a patient 
experiences an increase in disease activity during an attempted taper, the patient’s corticosteroid 
dose may be increased once, by up to 10 mg/day, but may not exceed the baseline dose.  
Corticosteroid dose must be stable for 8 weeks prior to Week 24 (i.e., no changes between 
Weeks 16 and 24) and for 12 weeks prior to Week 52 (i.e., no changes between Weeks 40 and 
52).  This design minimizes confounding of assessments at Week 24 and Week 52.
Throughout the trial, investigators should continue to assess benefit/risk for patients to remain in 
the trial and should consider discontinuing patients if sufficient clinical benefit is not observed 
with protocol permitted treatments.
Follow-up Period: Patients who complete the treatment period of the study through Week 52 
(Visit 16) are eligible to participate in the long-term extension (LTE), Study I4V-MC-JAIM
(JAIM). In some circumstances, due to COVID-19 related logistical issues, patients who were 
unable to complete Visit 16 in the protocol specified timeframe and had study drug temporarily 
interrupted, but otherwise completed the treatment period, may be eligible to participate in Study 
JAIM.  Patients who do not participate in the LTE, as well as those who discontinue JAIA study 
treatment early, will have a post-treatment follow-up visit (Visit 801) approximately 4 weeks 
after the last dose of investigational product.

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Abbreviations:  LD = last dose of investigational product; LTE = long-term extension; 
n = number of patients in each group; QD = once daily; V = visit; W = week
Figure JAIA.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIA.
5.2.
Number of Participants
Approximately 750 patients will be randomized for a total of 250 patients per treatment group.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
This study will be double-blinded and placebo-controlled to minimize bias.  The selection of 
placebo as a comparator for this study is warranted as there are few approved therapies for SLE 
and all patients in the study will be receiving concomitant SoC, including corticosteroids, 
antimalarials, and/or immunosuppressants. In order to minimize the confounding effects of 
concomitant medications, doses of antimalarials and immunosuppressants should remain stable 
during the treatment period (see Section 7.7).
The population studied will include patients with active disease and varying degrees of SLE 
organ involvement; however, patients with severe active lupus nephritis and active central 
nervous system (CNS) SLE are excluded as they would require aggressive treatment with 
medications that could confound the safety and/or efficacy results of the study.
The primary efficacy endpoint of SRI-4 is consistent with FDA and EU guidance (FDA 2010; 
EMA 2015) and follows regulatory precedent (FDA 2012) for assessing efficacy in SLE 
registration studies.  Furthermore, the SRI-4, as a composite index, detects overall improvements 
in disease activity (SLEDAI-2K component) while ensuring there is not worsening in other 
organ systems (BILAG and Physician’s Global Assessment components).  
Screening
Post-
Treatment
+ Option to enter LTE Study JAIM.
Treatment
Corticosteroid tapering permitted. 
Corticosteroid dose stable.
W-6
V1
W0
V2
W1
V3
W4
V4
W12
V6
W8
V5
W16
V7
W24
V9
W20
V8
W28
V10
W36
V12
W40
V13
W48
V15
W44
V14
W52
V16
W32
V11
LD+4W
V801
baricitinib 4 mg QD (n=250)
baricitinib 2 mg QD (n=250)
placebo QD (n=250)
All Patients
Randomization
Primary Endpoint
+
+
+

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Owing to the heterogeneity and natural course of SLE disease, a duration of 52 weeks is 
considered necessary to confirm efficacy, safety, and maintenance of response.  This duration 
also allows for a corticosteroid burst up to Week 12, for patients who enter the study with 
increased disease activity.  This design prevents premature discontinuation of patients from the 
study while minimizing potential confounding effects on efficacy assessments at Weeks 24 and 
52 (the primary endpoint).
5.5.
Justification for Dose
The 4-mg and 2-mg QD doses of baricitinib selected for this study are based on the Phase 2 SLE 
study, Study JAHH, and are additionally supported by PK, safety, and efficacy data for 
baricitinib in Phase 2 and Phase 3 RA studies and the Phase 2 psoriasis study.
In the Phase 2 SLE study, baricitinib 4-mg QD demonstrated statistically significant efficacy 
compared to placebo across several relevant measures, including remission of arthritis and/or 
rash (SLEDAI-2K), SRI-4, flare, and LLDAS.  Baricitinib 2-mg QD was numerically better than 
placebo across these measures, although the results were not statistically significant.  Dose 
response patterns favoring baricitinib 4-mg were evident across measures and improvement was 
observed for both doses in patient-reported outcomes including worst pain and worst joint pain.  
Pharmacokinetic/pharmacodynamic (PK/PD) modeling suggests the maximum response after 
dosing with 2-mg was not attained by 24 weeks.  Therefore, there is potential that baricitinib 
2-mg will also demonstrate efficacy at Week 52.  No notable safety findings emerged compared 
to the results from baricitinib studies for other indications.
In Phases 2 and 3 RA studies, baricitinib 4-mg QD has demonstrated consistent efficacy; 
baricitinib 2-mg QD was also effective, but was less consistent than 4-mg QD across measures of 
efficacy and patient populations.  Both doses were acceptably safe and well tolerated in the 
context of the efficacy observed and the benefit/risk profiles of other disease-modifying 
antirheumatic drugs.  There was no substantial increase in efficacy noted with doses higher than 
4-mg, where studied.
In the Phase 2 psoriasis study, baricitinib doses between 4-mg and 10-mg were associated with 
statistically significant reductions in measures of disease activity, with greater efficacy at the 
higher doses.  The 2-mg dose did show numeric improvements in efficacy compared with 
placebo.  The 8-mg and 10-mg doses were associated with a higher rate of AEs related to 
laboratory abnormalities (decreases in hemoglobin, neutrophils, and lymphocytes), while the 
2-mg and 4-mg dose groups had a pattern of AEs similar to placebo.
Dose Adjustment for Renal Impairment
As detailed in the IB, baricitinib exposure increases with decreased renal function (Study 
I4V-MC-JADL [JADL]).  Based on PK simulations, dose adjustment is not required for patients 
with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2.  Patients with eGFR 
<60 mL/min/1.73 m2 at screening who are randomized to the 4-mg dose will receive a dose of 
2-mg QD, which will ensure that exposures do not exceed those of the 4-mg QD dose in patients 

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with eGFR ≥60 mL/min/1.73 m2.  For patients randomized to the 2-mg dose, there will be no 
dose reduction based on renal function. 
See Section 7.2.2 for method of treatment assignment in patients with renal impairment.

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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
Study investigator(s) will review patient history and screening test results at Visit 1 and Visit 2 to 
determine if the patient meets all inclusion and none of the exclusion criteria to qualify for 
randomization in the study. All screening activities must be completed and reviewed before the 
patient is randomized.
Patient eligibility will be reviewed and must be confirmed by an eligibility review 
committee prior to randomization.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria:
Type of Patient and Disease Characteristics
[1]
Are at least 18 years of age.
[2]
Have a clinical diagnosis of SLE at least 24 weeks prior to screening.
[3]
Have documentation of having met at least 4 of 11 Revised Criteria for 
Classification of Systemic Lupus Erythematosus according to the 1997 Update of 
the 1982 ACR criteria for classification of SLE (Tan et al. 1982; Hochberg et al. 
1997) prior to randomization.
[4]
Have 1 or more of the following as assessed by the central lab during screening:  a 
positive antinuclear antibody (ANA; titer ≥1:80), and/or a positive anti-dsDNA, 
and/or a positive anti-Smith (anti-Sm).  Patients with an ANA <1:80 at screening 
with documentation of a historical ANA ≥1:80 may be eligible, as assessed by the 
eligibility review committee.
Note:  The ANA, anti-dsDNA, and anti-Smith measurements may be repeated by 
the central lab once during the screening period, and the value resulting from 
repeat testing may be accepted for enrollment eligibility if it meets the eligibility 
criterion.
[5]
Have a total SLEDAI-2K score ≥6 during screening, with at least 4 points 
attributed to clinical items (not including items requiring laboratory value 
assessment).  SLEDAI-2K items requiring laboratory values should be assessed 
based on the results from the labs drawn during the screening period.
[6]
Have a clinical SLEDAI-2K score ≥4 at Baseline (Visit 2); not including any 
items requiring laboratory value assessment. 
[7]
Have at least 1 BILAG A score or 2 BILAG B scores during the screening period.  
BILAG items requiring laboratory values should be assessed based on the results 
from the labs drawn during the screening period.

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Prior/Concomitant Therapy
[8]
Are receiving at least one of the following SoC medications for SLE:
a.
A single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine) 
at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).
b. A single immunosuppressant (such as methotrexate [MTX], azathioprine, 
mycophenolate, tacrolimus, leflunomide, cyclosporine) at a stable therapeutic
dose for at least 8 weeks prior to screening (Visit 1).
c.
An oral corticosteroid, initiated at least 4 weeks prior to screening (Visit 1), at 
a stable dose ≤ 40 mg/day prednisone (or equivalent) for at least 2 weeks prior 
to screening (Visit 1) and through baseline (Visit 2).  If the patient is not 
receiving an antimalarial or immunosuppressant, the dose of corticosteroid 
must be ≥ 7.5 mg/day prednisone (or equivalent).
Patient Characteristics
[9]
Male or nonpregnant, nonbreastfeeding female patient
a.
Patients of child-bearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex relationship 
(as part of their preferred and usual lifestyle) must agree to either remain 
abstinent or stay in a same-sex relationship without sexual relationships with 
the opposite sex.  
b. Total abstinence is defined as refraining from intercourse during the entirety 
of the study and for at least 1 week following the last dose of investigational 
product.  Periodic abstinence such as calendar, ovulation, symptothermal, 
post-ovulation methods and withdrawal are not acceptable methods of 
contraception.
c.
Otherwise, patients of childbearing potential must agree to use 2 effective 
methods of contraception, where at least 1 form is highly effective, for the 
entirety of the study and for at least 1 week following the last dose of 
investigational product.
d. The following contraception methods are considered acceptable (the patient 
should choose 2, and 1 must be highly effective [defined as less than 1% 
failure rate per year when used consistently and correctly]):

Highly effective birth control methods:  

Combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:  oral, 
intravaginal, or transdermal

Progestogen- only containing hormonal contraception associated 
with inhibition of ovulation:  oral, injectable, or implantable

intrauterine device (IUD)/intrauterine hormone-releasing system 
IUS)

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
vasectomized male (with appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate).

Effective birth control methods:

Male or female condom with spermicide.  It should be noted that 
the use of male and female condoms as a double barrier method is 
not considered acceptable due to the high failure rate when these 
methods are combined.

Diaphragm with spermicide

Cervical sponge

Cervical cap with spermicide
Note:  When local guidelines concerning highly effective or effective 
methods of birth control differ from the above, the local guidelines must 
be followed.
Patients of non‒child-bearing potential are not required to use birth control and 
they are defined as:

Women who are infertile due to surgical sterilization (hysterectomy, 
bilateral oophorectomy, or tubal ligation)

Post-menopausal – defined either as

A woman at least 50 years of age with an intact uterus, not on 
hormone therapy, who has either
o
Cessation of menses for at least 1 year
o
At least 6 months of spontaneous amenorrhea with 
follicle-stimulating hormone >40 mIU/mL

Women aged 55 years or older who are not on hormone therapy, and 
who have had at least 6 months of spontaneous amenorrhea

Women aged 55 years or older who have a diagnosis of menopause
Informed Consent
[10] Must read and understand the informed consent approved by Eli Lilly and 
Company (Lilly), or its designee, and the institutional review board (IRB)/ethics 
review board (ERB) governing the site, and provide written informed consent. 

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6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
Medical Conditions
[11] Have severe active lupus nephritis defined clinically and/or by histologic evidence
of proliferative glomerulonephritis on renal biopsy (if available) within the 24 
weeks prior to screening, or urine protein/creatinine ratio >200 mg/mmol (as an 
estimate of approximate proteinuria >2 g/day) or eGFR (Modification of Diet in 
Renal Disease [MDRD]) <40 mL/min/1.73 m2 at screening, or as determined by 
the eligibility review committee.
Note:  The lab measurements related to lupus nephritis may be repeated once by 
the central lab during the screening period, and the values resulting from repeat 
testing may be accepted for enrollment eligibility if they meet the eligibility 
criterion.
[12] Have active CNS lupus as defined by ACR nomenclature for neuropsychiatric 
lupus syndromes and as captured by SLEDAI-2K (seizure, psychosis, organic 
brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, and 
cerebrovascular accident).
[13] Have active fibromyalgia that, in the investigator’s opinion, would make it 
difficult to appropriately assess SLE activity for the purposes of this study.
[14] Have been treated for or had an active occurrence of a systemic inflammatory 
condition other than SLE such as, but not limited to, RA, juvenile chronic 
arthritis, spondyloarthropathy, Crohn’s disease, ulcerative colitis, or psoriatic 
arthritis within the 12 weeks prior to screening.  Patients with secondary 
Sjögren’s syndrome are not excluded.
[15] Have had any major surgery within 8 weeks prior to screening or will require 
major surgery during the study that, in the opinion of the investigator in 
consultation with Lilly or its designee, would pose an unacceptable risk to the 
patient.
[16] Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the 
investigator, are clinically significant and indicate an unacceptable risk for the 
patient’s participation in the study.
[17] Have experienced any of the following within 12 weeks of screening:  VTE
(DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic 
heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
[18] Have a history of recurrent (≥ 2) VTE (DVT/PE).
[19] Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, 
endocrine, hematological, neurological, or neuropsychiatric disorders or any other 
serious and/or unstable illness that in the opinion of the investigator, could 
constitute an unacceptable risk when taking investigational product or interfere 
with the interpretation of data.

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[20] Have a history of lymphoproliferative disease; have signs or symptoms suggestive 
of possible lymphoproliferative disease, including lymphadenopathy or 
splenomegaly (other than primarily due to SLE); have active primary or recurrent 
malignant disease; or have been in remission from clinically significant 
malignancy for <5 years prior to randomization.
The following may be exempted: 
a.
Patients with cervical carcinoma in situ that has been resected with no evidence of
recurrence or metastatic disease for at least 3 years may participate in the study.
b. Patients with basal cell or squamous epithelial skin cancers that have been completely 
resected with no evidence of recurrence for at least 3 years may participate in the 
study.
[21] Have a current or recent (<4 weeks prior to randomization) clinically serious 
viral, bacterial, fungal, or parasitic infection or any other active or recent infection 
that in the opinion of the investigator, would pose an unacceptable risk to the 
patient if participating in the study.
Note:  For example, a recent viral upper respiratory tract infection or 
uncomplicated urinary tract infection need not be considered clinically serious.
[22] Have symptomatic herpes simplex at the time of randomization.
[23] Have had symptomatic herpes zoster infection within 12 weeks prior to 
randomization.
[24] Have a history of disseminated/complicated herpes zoster (for example, 
ophthalmic zoster or CNS involvement).
[25] Have a positive test for hepatitis B virus (HBV) defined as:
a.
positive for hepatitis B surface antigen (HBsAg), or
b. positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B 
virus deoxyribonucleic acid (HBV DNA)
Note:  Patients who are HBcAb-positive and HBV DNA-negative may be 
enrolled in the study but will require additional HBV DNA monitoring during 
the study.
[26] Have hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV
ribonucleic acid [RNA]-positive).
Note:  Patients who have documented anti-HCV treatment for a past HCV 
infection AND are HCV RNA-negative may be enrolled in the study.
[27] Have evidence of HIV infection and/or positive HIV antibodies.
[28] Have had household contact with a person with active TB and did not receive 
appropriate and documented prophylaxis for TB..
[29] Have evidence of active TB or latent TB

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a.
Have evidence of active TB, defined in this study as the following:

Positive purified protein derivative (PPD) test (≥5 mm induration between 
approximately 2 and 3 days after application, regardless of vaccination 
history), medical history, clinical features, and abnormal chest x-ray at 
screening.

QuantiFERON®-TB Gold test or T-SPOT® TB test (as available and if compliant 
with local TB guidelines) may be used instead of the PPD test.  Patients are 
excluded from the study if the test is not negative and there is clinical evidence of 
active TB.
Exception:  patients with a history of active TB who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was 
completed, have no clinical features of active TB, and have a screening chest x-ray 
with no evidence of active TB may be enrolled if other entry criteria met.  Such 
patients would not be required to undergo the protocol-specific TB testing for PPD, 
QuantiFERON®-TB Gold test, or T-SPOT®.TB test but must have a chest x-ray at 
screening (i.e., chest imaging performed within the past 6 months will not be 
accepted).
b. Have evidence of untreated/inadequately or inappropriately treated latent TB, 
defined in this study as the following:

Positive PPD test, no clinical features consistent with active TB, and a 
chest x-ray with no evidence of active TB at screening; or

If the PPD test is positive and the patient has no medical history or chest 
x-ray findings consistent with active TB, the patient may have a 
QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if 
compliant with local TB guidelines).  If the test results are not negative, 
the patient will be considered to have latent TB (for purposes of this 
study); or 

QuantiFERON®-TB Gold test or T- SPOT®.TB test (as available and if 
compliant with local TB guidelines) may be used instead of the PPD test.  
If the test results are positive, the patient will be considered to have latent 
TB.  If the test is not negative, the test may be repeated once within 
approximately 2 weeks of the initial value.  If the repeat test results are 
again not negative, the patient will be considered to have latent TB (for 
purposes of this study).
Exception:  Patients who have evidence of latent TB may be enrolled if he or 
she completes at least 4 weeks of appropriate treatment prior to randomization 
and agrees to complete the remainder of treatment while in the trial.

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Exception:  Patients with a history of latent TB who have documented 
evidence of appropriate treatment, have no history of re-exposure since their 
treatment was completed, have no clinical features of active TB, and have a 
screening chest x-ray with no evidence of active TB may be enrolled if other 
entry criteria met.  Such patients would not be required to undergo the 
protocol-specific TB testing for PPD, QuantiFERON®-TB Gold test, or 
T-SPOT®.TB test but must have a chest x-ray at screening (i.e., chest 
imaging performed within the past 6 months will not be accepted).
[30] Have received parenteral [i.e., intravenous, intramuscular, intra-articular] 
corticosteroids within 6 weeks of screening (Visit 1), or are expected to require 
parenteral corticosteroids during the study.
[31] Have received any of the following medications: 
a.
Biologic treatments for immunologic disease such as etanercept, infliximab, 
certolizumab, adalimumab, golimumab, tocilizumab, abatacept, ustekinumab, 
ixekizumab, secukinumab, or anakinra within 4 weeks of screening.
b. Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab 
(or another anti-IFN therapy) within 12 weeks of screening.
c.
Rituximab, any other B cell depleting therapies, or intravenous 
immunoglobulin (IVIg) within 24 weeks of screening.
[32] Have received a JAK inhibitor or TYK-2 inhibitor.
[33] Have been treated with probenecid that cannot be discontinued for the duration of 
the study.
[34] Have received plasmapheresis within 12 weeks of screening.
[35] Have been exposed to a live vaccine within 12 weeks of randomization or are 
expected to need/receive a live vaccine during the course of the study (with the 
exception of herpes zoster vaccination).
Note:  All patients who have not previously received the herpes zoster vaccine by 
screening will be encouraged (per local guidelines) to do so prior to randomization; 
vaccination with live herpes zoster vaccine must occur >4 weeks prior to randomization 
and start of investigational product.  Patients will not be randomized if they were exposed 
to a live herpes zoster vaccination within 4 weeks of planned randomization.  
Investigators should review the vaccination status of their patients and follow the local 
guidelines for vaccination of patients ≥18 years of age with nonlive vaccines intended to 
prevent infectious disease prior to entering patients into the study.
[36] Are currently enrolled in or have discontinued within 4 weeks of screening from, 
any other clinical trial involving an investigational product or nonapproved use of 
a drug or device or any other type of medical research judged not to be 
scientifically or medically compatible with this study.

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[37] Have previously completed or been randomized and withdrawn from this study or 
have received baricitinib in any other study.
Diagnostics Assessments
[38] Have screening laboratory test values, including thyroid-stimulating hormone 
(TSH), outside the reference range for the population that, in the opinion of the 
investigator, pose an unacceptable risk for the patient’s participation in the study. 
Patients who are receiving thyroxine as replacement therapy may participate in 
the study, provided stable therapy has been administered for ≥12 weeks and TSH 
is within the laboratory’s reference range.  Patients who have TSH marginally 
outside the laboratory’s normal reference range and are receiving stable thyroxine 
replacement therapy may participate if the treating physician has documented that 
the thyroxine replacement therapy is adequate for the patient.
[39] Have any of the following specific abnormalities on screening laboratory tests
from the central laboratory:
b. ALT or AST >2 x ULN
c.
alkaline phosphatase (ALP) ≥2 x ULN
d. total bilirubin ≥1.5 x ULN
e.
hemoglobin <9 g/dL (90.0 g/L)
f.
total white blood cell count <2500 cells/µL (<2.50 x 103/µL or <2.50 GI/L)
g. neutropenia (absolute neutrophil count [ANC] <1200 cells/µL) 
(<1.20 x 103/µL or <1.20 GI/L)
h. lymphopenia (lymphocyte count <500 cells/µL) (<0.50 x 103/µL or 
<0.50 GI/L)
i.
thrombocytopenia (platelets <50,000 cells/µL) (<50 x 103/µL or <50 GI/L)
In the case of any of the aforementioned laboratory abnormalities, the tests may 
be repeated once by the central laboratory during screening, and values resulting 
from repeat testing may be accepted for enrollment eligibility if they meet the 
eligibility criterion.
Other Exclusions
[40] Are largely or wholly incapacitated permitting little or no self-care, such as being 
bedridden or confined to wheelchair.
[41] In the opinion of the investigator, are at an unacceptable risk for participating in 
the study.
[42] Have donated more than a single unit of blood within 4 weeks prior to screening 
or intend to donate blood during the course of the study.

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[43] Have a history of intravenous drug abuse, other illicit drug abuse, or chronic 
alcohol abuse within the 2 years prior to screening or are concurrently using, or 
expected to use during the study, illicit drugs (including marijuana).
[44] Are unable or unwilling to make themselves available for the duration of the 
study and/or are unwilling to follow study restrictions/procedures.
[45] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[46] Are Lilly or Incyte employees or their designee.
6.3.
Lifestyle Restrictions
Study participants should be instructed not to donate blood or blood products during the study or 
for 30 days following the last dose of investigational product.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened one time.  The interval between initial screening and rescreening Visit 1 should be at 
least 4 weeks.  When rescreening is performed the individual must sign a new ICF, repeat all 
screening procedures as described in the Schedule of Activities, and will be assigned a new 
identification number.

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7. Treatments
7.1.
Treatments Administered
This study involves a comparison of baricitinib tablets 4-mg or 2-mg administered orally QD 
with placebo tablets administered orally QD. Table JAIA.3 shows the treatment regimens.
Table JAIA.3.
Treatment Regimens
Treatment Group
Treatments Administered
Day 1 through Day 365
Baricitinib 4-mg QDa
1 baricitinib 4-mg tablet and 1 placebo tablet matching baricitinib 2-mg
Baricitinib 2-mg QD
1 baricitinib 2-mg tablet and 1 placebo tablet matching baricitinib 4-mg
Placebo QD
2 placebo tablets: 1 matching baricitinib 4-mg and 1 matching baricitinib 2-mg
Abbreviations:  QD = once daily.
a
Patients with estimated glomerular filtration rate <60 mL/min/1.73 m2 at screening who are randomized to the 
4-mg dose will receive a dose of 2-mg QD.
The investigator or his or her designee is responsible for the following:

explaining the correct use of the investigational agent(s) to the patient

verifying that instructions are followed properly

maintaining accurate records of investigational product dispensing and collection

at the end of the study returning all unused medication to Lilly, or its designee, 
unless the sponsor and sites have agreed all unused medication is to be destroyed 
by the site, as allowed by local law
7.1.1. Packaging and Labelling
Lilly (or its designee) will provide the following primary study materials:

tablets containing 4-mg of baricitinib

tablets containing 2-mg of baricitinib

tablets containing placebo to match 4-mg baricitinib

tablets containing placebo to match 2-mg baricitinib
Investigational product will be dispensed to the patient at the principal investigator’s study site.  
Investigational product packaging will contain enough tablets for the longest possible interval
between visits.
Investigational product will be labeled according to the country’s regulatory requirements.  
Patients will be instructed to take 2 tablets, one tablet from each bottle, each day. 

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All investigational products will be stored, inventoried, reconciled, and destroyed according to
applicable regulations. Investigational products will be supplied by Lilly or its representative in
accordance with current Good Manufacturing Practices and will be supplied with lot numbers,
expiry dates, and certificates of analysis (as applicable).
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized in a 1:1:1 ratio (baricitinib 
4-mg; baricitinib 2-mg; placebo) to double-blind treatment at Visit 2.  Randomization will be 
stratified by disease activity (total SLEDAI-2K at screening <10; ≥10), corticosteroid dose (<10 
mg/day; ≥10 mg/day prednisone or equivalent), and region (defined in the SAP).
Assignment to treatment groups will be determined by a computer-generated random sequence 
using an interactive web-response system (IWRS).  The IWRS will be used to assign packages 
containing double-blind investigational product to each patient, starting at Visit 2 (Week 0), and 
at each visit subsequent through Visit 15 (Week 48).  Each package of clinical trial material will 
supply sufficient study medication at least for the number of weeks between visits.  Site 
personnel will confirm that they have located the correct packages by entering a confirmation 
number found on the packages of investigational product into the IWRS before dispensing the 
packages to the patient.
7.2.1. Selection and Timing of Doses
Investigational product will be provided to patients following randomization at Visit 2 (Week 0).
Two tablets (1 tablet from each bottle) should be taken orally each day, without regard to food 
and, if possible, at approximately the same time every day. Special timing considerations of 
administration of investigational product relative to PK sample collection at study visits are 
described in Section 9.5.
7.2.2. Dose Adjustment for Renal Impairment
The dose adjustment for renal impairment will be managed by IWRS to ensure maintenance of 
the treatment blind.  The eGFR value from screening will be entered into IWRS at Visit 2, and 
IWRS will assign the treatment doses accordingly. 

Patients with documented renal impairment (defined as screening eGFR ≥40 to 
<60 mL/min/1.73 m2), who are randomized to active treatment (either to the 
baricitinib 4-mg arm or the baricitinib 2-mg arm) will receive a baricitinib 2-mg QD 
dose by the IWRS. 

No dose adjustment will be made for patients with screening eGFR ≥60 mL/min/1.73 
m2.
The rationale of dose adjustment for patients with documented renal impairment is detailed in 
Section 5.5.
Interruption criteria due to eGFR during the treatment period is discussed in Section 8.1.1.

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7.3.
Blinding
This is a double-blind study.  To preserve the blinding of the study, a minimum number of Lilly 
personnel who are not directly involved with investigational sites will see the randomization 
table and treatment assignments before the study is complete.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted.  Patient safety must always be the first 
consideration in making such a determination.  If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor-designated medical 
monitor prior to unblinding a patient’s treatment assignment unless this could delay emergency 
treatment of the patient.  If a patient’s treatment assignment is unblinded, Lilly must be notified 
immediately.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment. All 
calls resulting in an unblinding event are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or patient is unblinded, the patient 
must be discontinued from the study.  In cases where there are ethical reasons to have the patient 
remain in the study, the investigator must obtain specific approval from a Lilly-designated 
medical monitor for the patient to continue in the study.
7.4.
Dosage Modification
During this study, treatment assignment and dose adjustment of investigational product will be 
followed strictly as indicated in Sections 7.1 and 7.2.
See Section 7.7 for permitted concomitant therapy.
7.5.
Preparation/Handling/Storage/Accountability
All investigational product (used and partially used) will be returned to the sponsor or destroyed
at site level with the sponsor’s written approval. In some cases, sites may destroy the material if
during the investigative site selection, the evaluator has verified and documented that the site has
appropriate facilities and written procedures to dispose of clinical trial materials.
Storage and handling instructions are provided on the investigational product packaging and 
should be followed.
7.6.
Treatment Compliance
Patient compliance with investigational product will be assessed at Visit 3 through Visit 16 and 
at Early Termination during the treatment period by counting returned tablets. Deviations from 
the prescribed dosage regimen should be recorded in the electronic case report form (eCRF).
A patient treated with baricitinib or placebo will be considered significantly noncompliant if he 
or she misses >20% of the prescribed doses during the treatment period, unless the patient’s 
investigational product was withheld by the investigator for safety reasons.

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Similarly, a patient will be considered significantly noncompliant if he or she is judged by the 
investigator to have intentionally or repeatedly taken more than the prescribed amount of 
investigational product. Patients found to be noncompliant with the investigational product 
should be assessed to determine the reason for noncompliance and educated and/or managed as 
deemed appropriate by the investigator to improve compliance.
7.7.
Concomitant Therapy
Patients will maintain their usual medication regimen for SLE and for any other concomitant 
diseases throughout the study unless specifically excluded in the protocol (see Section 6.2, 
Exclusion Criteria).  Patients taking these medications should be on chronic stable doses at the 
time of randomization, as specified by the Inclusion Criteria (Section 6.1, Inclusion Criterion 
[8]).  
Permitted concomitant background standard of care medications for SLE include:

A single antimalarial (such as hydroxychloroquine, chloroquine, quinacrine) 
at a stable therapeutic dose for at least 8 weeks prior to screening (Visit 1).  
Doses should remain stable throughout the treatment period.

A single immunosuppressant (such as MTX, azathioprine, mycophenolate, 
tacrolimus, leflunomide, cyclosporine) at a stable therapeutic dose for at least 
8 weeks prior to screening (Visit 1).  Doses should remain stable throughout 
the treatment period.

An oral corticosteroid, initiated at least 4 weeks prior to screening (Visit 1), at 
a stable dose ≤40 mg/day prednisone (or equivalent) for at least 2 weeks prior 
to screening (Visit 1) and through baseline (Visit 2).  If the patient is not 
receiving an antimalarial or immunosuppressant, the dose of corticosteroid 
must be ≥7.5 mg/day prednisone (or equivalent).  See Section 7.7.1 for 
permitted changes to corticosteroid dosing.
Any changes to the patient’s medication must be discussed with the investigator.  Treatments for 
SLE or other concurrent illnesses may be reduced for safety reasons. Patients should be 
instructed to consult the investigator or other appropriate study personnel at the site before taking 
any new medications or supplements.
Additional medications are to be avoided during the study unless required to treat an AE or for 
the treatment of an ongoing medical problem.  Between Weeks 0 and 12 and between Weeks 24 
and 36, steroids for non-SLE reasons may be permitted on a short-term (no more than 14 days) 
basis.  Patients must be back to prior dose within 14 days (or by Week 14/Week 38) from the 
initiation of the high-dose steroids for non-SLE reasons (whichever is sooner).  If the need for 
concomitant medication arises, inclusion or continuation of the patient may be at the discretion 
of the investigator after consultation with Lilly or its designee. Any additional medication 
whether prescription or over-the-counter, used at baseline and/or during the course of the study 
must be documented in the eCRF with start and stop dates.

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7.7.1. Permitted Changes and Additions to Concomitant Therapy
Changes to corticosteroid dosing are permitted during the treatment period as follows.
Corticosteroid Tapering
Investigators are encouraged to taper corticosteroids according to clinical practice with a goal of 
≤7.5 mg/day prednisone (or equivalent) by Week 40 (Visit 13).
Tapering may occur from Week 0 through Week 16 and from Week 24 (after completion of 
Visit 9) through Week 40 (see Figure JAIA.1).  In most cases, tapering should not be considered 
for at least 4 weeks after randomization, consistent with clinical practice.  If a patient 
experiences an increase in disease activity during an attempted taper, the patient’s corticosteroid 
dose may be increased once by up to 10 mg/day or up to the baseline dose (whichever is lower).  
The corticosteroid dose may not exceed the baseline dose.  
Corticosteroid dose must be stable for 8 weeks prior to Week 24 (i.e., no changes between 
Weeks 16 and 24) and for 12 weeks prior to Week 52 (i.e., no changes between Weeks 40 and 
52).  This design minimizes confounding of assessments at Week 24 and Week 52 (see 
Figure JAIA.1).
Corticosteroid Burst
A single corticosteroid burst is permitted for patients with increased disease activity early the 
treatment period. 
During Weeks 0 through 12, patients with intolerable disease activity may receive a single 
corticosteroid burst of up to 40 mg/day oral prednisone for up to 7 days (in addition to the 
regular dose, up to a maximum of 60 mg/day prednisone or equivalent total daily dose).  The 
patient must be at or below their preburst corticosteroid dose by the end of the 7-day burst 
period, which may not extend beyond Week 12.  As an alternative to the oral corticosteroid 
burst, a single 80-mg intramuscular dose of methylprednisone (or equivalent) may be given 
during Weeks 0 through 11.
7.7.2. Prohibited Changes in Concomitant Therapy
Initiation of or increase in dose of an antimalarial or immunosuppressant is not permitted during 
the treatment period.  Patients requiring an initiation or increase above baseline dose of 
antimalarials or immunosuppressants, as defined in the SAP, during the treatment period will be 
discontinued from the study drug (see Section 8.1.2). 
Patients requiring an increase above the baseline dose of corticosteroid for SLE during the 
treatment period, other than the permitted burst, as defined in the SAP, will be discontinued from 
study drug (see Section 8.1.2).

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7.8.
Treatment after the End of the Study
7.8.1. Study Extensions
Patients who complete this study through Week 52 (Visit 16) may be eligible to participate in 
Study JAIM, if enrollment criteria for Study JAIM are met.  In some circumstances, due to 
COVID-19 related logistical issues, patients who were unable to complete Visit 16 in the 
protocol specified timeframe and had study drug temporarily interrupted, but otherwise 
completed the treatment period, may be eligible to participate in Study JAIM.
7.8.2. Treatment after Study Completion
Baricitinib will not be made available after conclusion of the study to patients except as 
described in Section 7.8.1.

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Temporary Interruption of Investigational Product
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or abnormal laboratory values that may have an unclear relationship to investigational product.  
It is recommended that the investigator consult with Lilly (or its designee) before temporarily 
interrupting therapy for reasons other than those defined in Table JAIA.4.  Retest timing and 
frequency is at the investigator’s discretion.
Investigational product that was temporarily interrupted because of an AE or abnormal 
laboratory value not specifically covered in Table JAIA.4 may be restarted at the discretion of 
the investigator.  Investigational product must be held in the following situations and may only 
be resumed as noted in the table.

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Table JAIA.4.
Criteria for Temporary Interruption of Investigational Product
Hold Investigational Product if the Following 
Abnormalities Occur:
Investigational Product May be Resumed When:
WBC count <2000 cells/µL
(<2.00 x 103/µL or <2.00 GI/L)
WBC count 2500 cells/µL
(≥2.50 x 103/µL or ≥2.50 GI/L)
ANC <1000 cells/L 
(<1.00 x 103/µL or <1.00 GI/L)
ANC ≥1200 cells/µL
(≥1.2 x 103/µL or ≥1.2 GI/L)
Lymphocyte count <300 cells/µL
(<0.30 x 103/µL or <0.30 GI/L)
Lymphocyte count 500 cells/µL
(≥0.50 x 103/µL or ≥0.50 GI/L)
Platelet count <25,000/µL
(<25 x 103/µL or <25 GI/L)
Platelet count 50,000/µL
(≥50 x 103/µL or ≥50 GI/L)
eGFR <40 mL/min/1.73 m2 for patients with
screening eGFR ≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 for patients with 
screening eGFR ≥40 to <60 mL/min/1.73 m2
eGFR 40 mL/min/1.73 m2 
ALT or AST >5x ULN
ALT and AST return to <2 x ULN, and IP is not considered 
to be the cause of enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 9 g/dL (≥90.0 g/L)
Symptomatic herpes zoster
All skin lesions have crusted and are resolving
Infection that, in the opinion of the investigator, 
merits the IP being withhelda
Resolution of infection that, in the opinion of the 
investigator, merits the IP being restarted
Abbreviations:  ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; WBC = white blood cell.
a
Permanent discontinuation of IP should be considered for patients who develop a serious infection that, in the 
opinion of the investigator, would pose an unacceptable risk if IP were resumed.
8.1.2. Permanent Discontinuation from Study Treatment
Possible reasons leading to permanent discontinuation of investigational product:

Subject Decision
o
the patient requests to discontinue investigational product.

Investigator Decision
o
the investigator decides that the patient should be discontinued from 
investigational product.

Discontinuation due to a hepatic event or liver test abnormality.  Patients who are 
discontinued from investigational product due to a hepatic event or liver test abnormality 
should have additional hepatic safety data collected via eCRF.

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Discontinuation of the investigational product for abnormal liver tests should be
considered by the investigator when a patient meets one of the following conditions after 
consultation with the Lilly designated medical monitor:

ALT or AST >8 x ULN

ALT or AST >5 x ULN for more than 2 weeks after temporary 
interruption of investigational product

ALT or AST >3 x ULN and either total bilirubin level (TBL) >2 x ULN or 
international normalized ratio (INR) >1.5 

ALT or AST >3 x ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain, or tenderness, fever, rash, and/or eosinophilia 
(>5%)

alkaline phosphatase (ALP) >3 x ULN

ALP >2.5 x ULN and TBL >2 x ULN

ALP >2.5 x ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

Discontinuation due to other laboratory abnormalities:

white blood cell count <1000 cells/µL (1.00x103/µL or 1.00 GI/L)

absolute neutrophil count <500 cells/µL (0.50x103/µL or 0.50 GI/L)

lymphocyte count <200 cells/µL (0.20x103/µL or 0.20 GI/L)

hemoglobin <6.5 g/dL (<65.0 g/L).
Temporary interruption rules (see Section 8.1.1) must be followed where applicable.  For 
laboratory values that meet permanent discontinuation thresholds, investigational product should 
be discontinued.  However, if in the opinion of the investigator, the laboratory abnormality is due 
to intercurrent illness or another identified factor, laboratory tests may be repeated.  The 
investigator may be able to restart investigational product after consultation with the 
Lilly-designated medical monitor, only when the laboratory value meets resumption thresholds 
(Table JAIA.4) following the resolution of the intercurrent illness or other identified factor.
Discontinuation due to other circumstances:

pregnancy

malignancy (except for successfully treated basal cell or squamous epithelial skin 
cancers)

hepatitis B virus DNA is detected with a value above the lower limit of quantitation
(see Section 9.4.8). 

occurrence of a VTE (DVT/PE) during the study

serious infection that in the opinion of the investigator, merits the 
investigational product being discontinued

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
if the patient, for any reason, requires treatment with another therapeutic agent 
that may be effective for treatment of SLE that is listed in the exclusion 
criteria (see Section 6.2) or is noncompliant to the concomitant therapy 
requirements (see Section 7.7.2) during the study.  Discontinuation from the 
investigational product must occur prior to introduction of the new agent.
Throughout the trial, investigators should continue to assess benefit/risk for patients to remain in 
the trial and should consider discontinuing patients if sufficient clinical benefit is not observed 
with protocol allowed concomitant treatments.
If a patient prematurely discontinues investigational product for any reason, the patient is 
encouraged to remain in the study through Week 52 (Visit 16) and follow the regular visit 
schedule per Section 2 (Schedule of Activities).
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the sponsor or investigator identify a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study treatment unless there 
are extenuating circumstances that make it medically necessary for the patient to continue on 
study treatment.  If the investigator and the sponsor-designated medical monitor agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
sponsor-designated medical monitor to allow the inadvertently enrolled patient to continue in the 
study with or without treatment with investigational product. Safety follow up is as outlined in 
Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of the 
protocol.
8.2.
Discontinuation from the Study
Patients will be discontinued in the following circumstances:

Enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study

Participation in the study needs to be stopped for medical, safety, regulatory, 
or other reasons consistent with applicable laws, regulations, and good clinical 
practice (GCP)

Subject decision
o
The patient requests to be withdrawn from the study
Patients discontinuing from the study prematurely for any reason should complete AE and other 
safety follow-up as indicated in the Early Term Visit per Section 2 (Schedule of Activities), 
Section 9.2 (Adverse Events), and Section 9.4 (Safety) of this protocol and proceed to the 
post-treatment follow up period.

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8.3.
Lost to Follow-up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.

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9.
Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Primary Efficacy Assessment
The SRI-4 is a composite index used to assess disease activity in SLE.  The SLEDAI-2K 
component is used to capture clinically meaningful improvement in disease activity, while the 
BILAG and Physician’s Global Assessment of Disease Activity components ensure that the 
improvement in overall disease is not accompanied by disease worsening in other organ systems.  
The SRI-4 response is defined as follows:

Reduction of ≥4 points from baseline in SLEDAI-2K score (Section 9.1.1.1); and

No new BILAG A and no more than 1 new BILAG B disease activity scores
(Section 9.1.1.2); and

No worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in 
Physician’s Global Assessment of Disease Activity (Section 9.1.1.3).
9.1.1.1.
Systemic Lupus Erythematosus Disease Activity Index-2000
The SLEDAI-2K is a validated global disease activity instrument that focuses on high-impact 
disease manifestations across 9 organ systems.  It includes 24 clinical and laboratory variables 
with manifestations graded by the affected organ system.  CNS:  Seizure, Psychosis, Organic 
Brain Syndrome, Visual Disturbance, Cranial Nerve Disorder, Lupus Headache, cerebrovascular 
attack; Vascular:  Vasculitis; Musculoskeletal:  Arthritis, Myositis; Renal:  Urinary Casts, 
Hematuria, Proteinuria, Pyuria; Mucocutaneous:  Rash, Alopecia, Mucosal Ulcers; 
Cardiovascular and Respiratory:  Pleurisy, Pericarditis; Immunologic:  Low complement, 
Increased DNA Binding; Constitutional:  Fever; Hematologic:  Thrombocytopenia, Leukopenia.
9.1.1.2.
British Isles Lupus Assessment Group 2004 Index
The BILAG-2004 Index is a validated global disease activity index designed on the basis of the 
physician’s intention to treat (ITT), focusing on changes in disease manifestations (not present, 
improving, same, worse, or new) occurring in the last 4 weeks compared with the previous 
4 weeks. The instrument assesses 97 clinical signs, symptoms, and laboratory parameters across 
9 organ system domains:  constitutional, mucocutaneous, neuropsychiatric, musculoskeletal,
cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematology.  A BILAG A disease 
activity score is severe disease activity requiring high-dose oral or intravenous corticosteroids, 
immunomodulators, or high-dose anticoagulation along with high-dose corticosteroids or 

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immunomodulators.  A BILAG B disease activity score is moderate disease activity requiring 
low-dose oral corticosteroids, intramuscular or intra-articular corticosteroid injections, topical 
corticosteroids or immunomodulators, antimalarials, or symptomatic therapy.  BILAG C 
corresponds to stable mild disease, BILAG D is inactive disease that was active previously, and 
BILAG E indicates the system was never involved.
9.1.1.3.
Physician’s Global Assessment of Disease Activity
The Physician’s Global Assessment of Disease Activity is the physician’s assessment of the 
patient’s overall disease activity due to SLE, as compared with all possible patients with SLE. 
The Physician’s Global Assessment of Disease Activity is scored using a 100-mm Visual Analog 
Scale (VAS), where 0 mm (measured from the left starting point of the line) indicates no disease 
activity and 100 mm (measured from the left starting point of the line) indicates the most severe 
disease activity possible for all patients with SLE (or death). The Physician’s Global 
Assessment of Disease Activity score is indicated by making a vertical tick mark on the line 
between 0 and 100 mm. There are benchmarks of 0 (0 mm), 1 (33 mm), 2 (67 mm), and 3 (100 
mm) on the line corresponding to no, mild, moderate, and severe SLE disease activity, 
respectively.
9.1.2. Secondary and Exploratory Efficacy Assessments
Secondary efficacy assessments will include the following:
9.1.2.1.
Systemic Lupus Erythematosus Responder Index
The SRI-4 will be assessed at various time points up to Week 52.  For assessment description, 
see Section 9.1.1.  The SRI-5, -6, -7, and -8 will also be assessed at various time points up to 
Week 52, and are similar to the SRI-4 except they require a reduction of ≥5, 6, 7, or 8 points 
(respectively) from baseline in SLEDAI-2K score (Section 9.1.1.1).
9.1.2.2.
Systemic Lupus Erythematosus Disease Activity Index-2000
The SLEDAI-2K will be assessed at various time points up to Week 52.  For assessment 
description, see Section 9.1.1.
9.1.2.3.
British Isles Lupus Assessment Group 2004 Index
The BILAG-2004 Index will be assessed at various time points up to Week 52.  For assessment 
description, see Section 9.1.1.
9.1.2.4.
Physician’s Global Assessment of Disease Activity
The Physician’s Global Assessment of Disease Activity will be assessed at various time points 
up to Week 52.  For assessment description, see Section 9.1.1.
9.1.2.5.
Safety of Estrogens in Lupus Erythematosus National Assessment 
(SELENA)-Systemic Lupus Erythematosus Disease Activity Index 
(SLEDAI) Flare Index
The SELENA-SLEDAI Flare Index (SFI) uses the SLEDAI score, disease activity scenarios, 
treatment changes, and Physician’s Global Assessment of Disease Activity to define 
mild/moderate and severe flares.  The index takes into account the absolute change in total 

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scores, new or worsening symptoms, and increases in medication use or hospitalization due to 
the disease activity.
9.1.2.6.
Cutaneous Lupus Erythematosus Disease Area and Severity Index
The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a validated 
scale used to assess cutaneous manifestations of SLE consisting of 2 scores.  The first 
summarizes the activity of the disease while the second is a measure of the damage done by the 
disease.  Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane 
involvement, acute hair loss, and nonscarring alopecia.  Damage is scored in terms of 
dyspigmentation and scarring, including scarring alopecia.
9.1.2.7.
Lupus Low Disease Activity State
The LLDAS is defined as a low level of disease activity attained with or without use of low-dose 
steroids and/or tolerated standard maintenance doses of SoC medications.
9.1.2.8.
Tender/Swollen Joint Count (28 Joints)
The 28 joints to be examined and assessed as tender or not tender for tender joint count and as 
swollen or not swollen for swollen joint count include 14 joints on each side of the patient’s 
body: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 
interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees.
9.1.2.9.
Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index
The SLICC/ACR Damage Index is scored on 41 items representing damage to 12 organ systems.  
The index records damage occurring in patients with SLE regardless of its cause and includes 
specific comorbidities associated with SLE that may be due to treatment-related toxicity.
9.1.2.10. British Isles Lupus Assessment Group Based Composite Lupus 
Assessment 
The BICLA is a composite index used to assess disease activity in SLE.  The BILAG component 
is used to capture clinically meaningful improvement in disease activity, while the BILAG, 
SLEDAI-2K, and Physician’s Global Assessment of Disease Activity components ensure that the 
improvement in overall disease is not accompanied by disease worsening in other organ systems.  
The BICLA response is defined as follows:

Reduction of all baseline BILAG A to B/C/D and baseline BILAG B to C/D, and no 
BILAG worsening in other organ systems, where worsening is defined as ≥1 new BILAG 
A or ≥2 new BILAG B

No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase 
from baseline of >0 points in SLEDAI-2K

No worsening from baseline in participants' lupus disease activity, where worsening is 
defined by an increase ≥0.30 points on a 3-point PGA visual analogue scale (VAS)

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9.1.2.11. Health Outcomes and Quality of Life Measures
The self-reported questionnaires will be administered via either an electronic patient diary or via 
an electronic tablet as specified in the Schedule of Activities (Section 2) in countries where the 
questionnaires have been translated into the native language of the region and linguistically 
validated.
9.1.2.11.1.Worst Pain Numeric Rating Scale 
The Worst Pain Numerical Rating Scale (NRS) is a single-item, patient-administered, 11-point 
horizontal scale anchored at 0 and 10, with 0 representing “no pain” and 10 representing “pain as 
bad as you can imagine.” Overall severity of a patient’s pain is indicated by selecting the number 
that best describes the worst level of pain in the last 24 hours. Data will be captured on a daily 
electronic patient diary.
9.1.2.11.2.Worst Joint Pain Numeric Rating Scale
The Worst Joint Pain NRS is a single-item, patient-administered, 11-point horizontal scale 
anchored at 0 and 10, with 0 representing “no joint pain” and 10 representing “joint pain as bad 
as you can imagine.” Overall severity of a patient’s joint pain is indicated by selecting the 
number that best describes the worst level of joint pain in the last 24 hours.  Data will be 
captured on a daily electronic patient diary.
9.1.2.11.3.Worst Fatigue Numeric Rating Scale
The Worst Fatigue NRS is a single-item, patient-administered, 11-point horizontal scale 
anchored at 0 and 10, with 0 representing “no fatigue” and 10 representing “as bad as you can 
imagine.” Overall severity of a patient’s fatigue is indicated by selecting the number that best 
describes the worst level of fatigue in the last 24 hours.  Data will be captured on a daily 
electronic patient diary.
9.1.2.11.4.Joint Stiffness Duration
The Duration of Joint Stiffness patient-reported outcomes (PRO) is a single-item, 
patient-administered scale designed to capture information on the self-reported length of time, in 
minutes, that a patient’s joint stiffness lasted each day. Patients report the duration of time by 
entering the number of hours and minutes their joint stiffness lasted today. Data will be captured 
on a daily electronic patient diary.
9.1.2.11.5.Joint Stiffness Severity Numeric Rating Scale
The Joint Stiffness Severity NRS is a single-item, patient-administered, 11-point horizontal scale 
anchored at 0 and 10, with 0 representing “no joint stiffness” and 10 representing “joint stiffness 
as bad as you can imagine.” Overall severity of a patient’s joint stiffness is indicated by selecting 
the number that best describes the worst level of joint stiffness in the last 24 hours.  Data will be 
captured on a daily electronic patient diary.
9.1.2.11.6.Patient’s Global Impression of Severity
The Patient’s Global Impression of Severity is a single-item question asking the patient how they 
would rate their overall lupus symptoms over the last 24 hours.  The 5 categories of response 
range from “no symptoms” to “severe”.  Data will be captured on a daily electronic patient diary.

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9.1.2.11.7.Patient’s Global Impression of Change
The Patient’s Global Impression of Change is a single-item question asking the patient how they 
would rate their change in overall lupus symptoms since they started the study.  The 7 categories 
of response range from “very much better” to “very much worse.”  Data will be captured on an 
electronic tablet collected at site visits.
9.1.2.11.8.Medical Outcomes Short-Form 36-Item Health Survey Version 2 
(SF-36v2)
The SF-36v2 Acute measure is a subjective, generic, health-related quality of life instrument that
is patient-reported and consists of 36 questions covering 8 health domains: physical functioning,
bodily pain, role limitations due to physical problems, role limitations due to emotional
problems, general health perceptions, mental health, social function, and vitality. Each domain is
scored by summing the individual items and transforming the scores into a 0 to 100 scale with
higher scores indicating better health related quality of life. In addition, 2 summary scores, the
PCS and the MCS, will be evaluated based on the 8 SF-36v2 Acute domains. The acute version
of this instrument has a 1 week recall period (Brazier et al. 1992; Ware and Sherbourne 1992).
Data will be captured on an electronic tablet collected at site visits.
9.1.2.11.9.Functional Assessment of Chronic Illness Therapy–Fatigue Scale
The FACIT-Fatigue scale (Cella and Webster 1997) is a brief, 13-item, symptom-specific 
questionnaire that specifically assesses the self-reported severity of fatigue and its impact upon 
daily activities and functioning. The FACIT-Fatigue uses 0 (“not at all”) to 4 (“very much”) 
NRS to assess fatigue and its impact in the past 7 days. Scores range from 0 to 52 with higher 
scores indicating less fatigue. Data will be captured on an electronic tablet collected at site 
visits.
9.1.2.11.10. Work Productivity and Activity Impairment Questionnaire–Lupus 
The Work Productivity and Activity Impairment Questionnaire-Lupus (WPAI-Lupus) records 
impairment due to Lupus during the past 7 days.  The WPAI-Lupus consists of 6 items grouped 
into four domains, absenteeism (work time missed), presenteesism (impairment at work / 
reduced on-the-job effectiveness), work productivity loss (overall work impairment /absenteeism 
plus presenteeism), and activity impairment.  Scores are calculated as impairment percentages 
(Reilly et al. 1993) with higher scores indicating greater impairment and less productivity.  Data 
will be captured on an electronic tablet collected at site visits.
9.1.2.11.11. European Quality of Life–5 Dimensions–5 Levels
The European Quality of Life-5 Dimensions 5 Levels (EQ-5D 5L) is a standardized measure of 
health status in order to provide a simple, generic measure of health for clinical and economic 
appraisal.  The EQ-5D 5L consists of 2 components:  a descriptive system of the respondent’s 
health and a rating of his/her current health state using a 0- to 100-mm VAS.  The descriptive 
system comprises the following 5 dimensions:  mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression.  Each dimension has 5 levels:  no problems, slight 
problems, moderate problems, severe problems, and extreme problems.  The respondent is asked 
to indicate his or her health state by ticking (or placing a cross) in the box associated with the 
most appropriate statement in each of the 5 dimensions.  It should be noted that the numerals 1 to 

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5 have no arithmetic properties and should not be used as an ordinal score.  The VAS records the 
respondent’s self-rated health on a vertical VAS where the endpoints are labeled “best 
imaginable health state” and “worst imaginable health state.”  This information can be used as a 
quantitative measure of health outcome.  The EQ-5D 5L health states, defined by the EQ-5D 5L 
descriptive system, may be converted into a single summary index by applying a formula that 
essentially attaches values (also called weights) to each of the levels in each dimension (EuroQol 
Group 2015 [WWW]). Data will be captured on an electronic tablet collected at site visits.
9.1.3. Appropriateness of Assessments
All assessments and/or concepts included in this study are standard, widely used, and generally 
recognized as reliable, accurate, and relevant.
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves or stabilizes with 
appropriate diagnostic evaluation.  The frequency of follow-up evaluations of the AE is left to 
the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, except SLE, as it is the disease under treatment in the 
study.  In addition, site personnel will record any change in the condition(s) and any new 
conditions as AEs. Investigators should record the following via eCRF for each AE:  start date, 
stop date (if applicable), severity, and their assessment of the potential relatedness of each AE to 
protocol procedure or investigational product, via eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment or pathologies.
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device and/or study procedure and the AE.
The investigator answers yes/no when making this assessment.

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Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF, clarifying if possible, the circumstances 
leading to any dosage modifications, or discontinuations of treatment.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

important medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention 
to prevent one of the other outcomes listed in the definition above.
All AEs occurring after signing the ICF are recorded in the eCRF and assessed for serious 
criteria.  The SAE reporting to the sponsor begins after the patient has signed the ICF and has 
received investigational product.  However, if an SAE occurs after signing the ICF, but prior to 
receiving investigational product, the SAE should be reported to the sponsor according to
SAE-reporting requirements and timelines (see Section 9.2) if it is considered reasonably 
possibly related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a paper SAE form.  If alerts are issued via telephone, they are to be 
immediately followed with official notification on study-specific SAE forms.  The SAE form 
should be completed by the investigator, and submitted via fax to the Sponsor’s global patient 
safety department.  This form includes a fax cover page that is pre-populated with the 
appropriate fax number.  The 24-hour notification requirement refers to the initial SAE 
information and all follow-up SAE information.  Patients with a serious hepatic AE should have 
additional data collected using the eCRF.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient disposition CRF has been completed).  
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 or she considers the event reasonably possibly related to 
the study treatment or study participation, the investigator must promptly notify Lilly.

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9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidance or national regulatory requirements in participating countries 
require the reporting of SUSARs.  Lilly has procedures that will be followed for the 
identification, recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidance.
9.2.2. Adverse Events of Special Interest
Adverse events of special interest (AESIs) will include the following:

infections (including TB, herpes zoster, or opportunistic infections)

malignancies

hepatic events (see Section 9.4.9)

major adverse cardiac events (MACE) (see Section 9.4.10) 

venous thromboembolic events (DVT/PE) (see Section 9.4.10.1)
Sites will provide details on these AEs as instructed on the eCRF and may be asked for 
additional description by Lilly.
9.2.3. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
Refer to the IB.
9.4.
Safety
Any clinically significant findings from ECG testing, physical examination, vital signs 
measurements, or laboratory measurements that result in a diagnosis and that occur after the 
patient receives the first dose of study treatment should be reported to Lilly or its designee as an 
AE via eCRF.
9.4.1. Electrocardiograms
A single 12-lead standard ECG will be obtained locally at Visit 1 and read by a qualified 
physician (the investigator or qualified designee) at the site to determine whether the patient 
meets entry criteria.

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Electrocardiograms may be obtained at additional times, when deemed clinically necessary.
9.4.2. Vital Signs
For each patient, vital signs measurements (sitting blood pressure, heart rate, and temperature) 
should be conducted according to the Schedule of Activities (Section 2).  Subjects should be 
seated and relaxed with both feet on the floor for at least 5 minutes prior to taking measurements.  
Three replicate blood pressure readings should be made at each time point at approximately 
30- to 60-second intervals.  A single-pulse measurement should be taken simultaneously with at 
least one of the blood pressure readings.  Blood pressure and pulse measurements should be 
made using either automated or manual equipment.  If measurements are machine averaged, the 
average blood pressure reading should be recorded on the CRF.  If measurements are manual or 
the machine does not provide an average reading, then each individual reading should be 
recorded on the CRF.  Measurements should be made before any scheduled blood draws.  
Additional measurements of vital signs may be performed at the discretion of the investigator.
9.4.3. Physical Examination
For each patient, physical examinations will be conducted according to the Schedule of 
Activities (Section 2).  One complete physical examination (excluding pelvic and rectal 
examinations) will be performed at Visit 1 (Screening).  All remaining physical examinations 
throughout the study should include a symptom-directed physical examination.  A complete 
physical examination may be repeated at the investigator’s discretion at any time a patient 
presents with physical complaints.
9.4.4. Laboratory Tests
For each patient, laboratory tests detailed in (Appendix 2) should be conducted according to the 
Schedule of Activities (Section 2).
With the exception of laboratory test results that may unblind the study, Lilly or its designee will 
provide the investigator with the results of laboratory tests analyzed by a central vendor, if a 
central vendor is used for the clinical trial.
9.4.5. Columbia-Suicide Severity Rating Scale
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and 
frequency of suicidal ideation and/or behavior during the assessment period.  The scale includes 
suggested questions to solicit the type of information needed to determine if suicidal ideation 
and/or behavior occurred.  The C-SSRS is administered by an appropriately trained health care 
professional with at least 1 year of patient care/clinical experience.  The tool was developed by 
the National Institute of Mental Health trial group for the purpose of being a counterpart to the 
Columbia Classification Algorithm of Suicide Assessment categorization of suicidal events.  For 
this study, the scale has been adapted (with permission from the scale authors) to include only 
the portion of the scale that captures the occurrence of the 11 preferred ideation and behavior 
categories.

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The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the Self-Harm Follow-up Form.  The 
Self-Harm Follow-up Form is a series of questions that provides a more detailed description of 
the behavior cases.
9.4.6. 16-Item Quick Inventory of Depressive Symptomatology:  
Self-Report
The QIDS-SR16 is a self-administered, 16-item instrument intended to assess the existence and 
severity of symptoms of depression as listed in the American Psychiatric Association’s 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) (APA 2013).  A 
patient is asked to consider each statement as it relates to the way they have felt for the past 
7 days.  There is a 4-point scale for each item ranging from 0 to 3.  The 16 items corresponding 
to 9 depression domains are summed to give a single score ranging from 0 to 27, with higher 
scores denoting greater symptom severity.  The domains assessed by the instrument include 
(1) sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, (5) interest, 
(6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or hypersomnia), 
(8) decrease/increase in appetite/weight, and (9) psychomotor agitation/retardation.
9.4.7. Chest x-Ray and Tuberculosis Testing
A posterior-anterior view chest x-ray will be obtained locally at screening (Visit 1), unless 
results from chest imaging (other than ultrasound) obtained within 6 months prior to the study 
are available.  The chest x-ray will be reviewed by the investigator or his or her designee to 
exclude patients with active TB infection.  In addition, patients will be tested at screening (Visit 
1) for evidence of active or latent TB as described in the exclusion criteria, Section 6.2.
Investigators should follow local guidelines for monitoring patients for TB if a patient is at high 
risk for acquiring TB or reactivation of latent TB.
9.4.8. Hepatitis B Virus  DNA Monitoring
Hepatitis B virus DNA testing will be performed in enrolled patients who tested positive for 
HBcAb at screening.
Patients who are HBcAb-positive and HBV DNA-negative (undetectable) at Visit 1 will require 
HBV DNA monitoring every 3 months and at the patient’s last visit, regardless of their hepatitis 
B surface antibody (HBsAb) status.

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The following actions should be taken in response to HBV DNA test results:

If a single result is obtained with a value “below limit of quantitation,” the test 
should be repeated within approximately 2 weeks.

If the repeat test result is “target not detected,” monitoring may resume according 
to the study schedule.

If the patient has 2 or more test results with a value “below limit of quantitation”
during the study, HBV DNA testing should be performed approximately once per 
month for the remainder of the study and referral to a hepatologist is 
recommended.

If a result is obtained with a value above limit of quantitation at any time during 
the study, the patient will be permanently discontinued from investigational 
product (see to Section 8.1.2) and should be referred to a hepatology specialist 
immediately.
o
In selected cases, investigators may temporarily continue investigational 
product in accordance with current immunomodulator management in the 
setting of HBV DNA positivity.  This option may be considered in 
consultation with Lilly (or its designee) and after evaluation of individual 
patient risks and benefits.
9.4.9. Hepatic Safety Monitoring
If a study patient experiences elevated ALT ≥3 x ULN, ALP ≥2 x ULN, or elevated TBL 
≥2 x ULN, liver testing (Appendix 4) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor.  Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels. 
Discontinuation criteria of investigational products, either temporary interruption or permanent 
discontinuation, due to abnormal ALT, AST, TBL, or ALP, are detailed in Section 8.1.2.
Hepatic Safety Data Collection
Additional safety data should be collected via the eCRF if 1 or more of the following conditions 
occur: 

Elevation of serum ALT to ≥5 x ULN on 2 or more consecutive blood tests

Elevated serum TBL to ≥ 2 x ULN (except for cases of known Gilbert’s 
syndrome)

Elevation of serum ALP to ≥2 x ULN on 2 or more consecutive blood tests

Patient discontinued from treatment due to a hepatic event or abnormality of 
liver tests

Hepatic event considered to be a SAE

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9.4.10. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
The Lilly-designated medical monitor will monitor safety data throughout the course of the 
study.  Lilly will review SAEs within time frames mandated by company procedures.  The 
Lilly-designated medical monitor will, as is appropriate, consult with the functionally 
independent Global Patient Safety (GPS) therapeutic area physician or clinical scientist and 
periodically review trends in safety data and laboratory analytes.  Any concerning trends in 
frequency or severity noted by an investigator and/or Lilly or its designee may require further 
evaluation.
All deaths and SAE reports will be reviewed in a blinded manner by Lilly during the clinical 
trial.  These reports will be reviewed to ensure completeness and accuracy but will not be 
unblinded to Lilly during the clinical trial.  If a death or clinical AE is deemed serious, 
unexpected, and possibly related to investigational product, Lilly GPS will be unblinded for 
regulatory reporting and safety monitoring purposes.  These measures will preserve the integrity 
of the data collected during this trial and minimize any potential for bias while providing for 
appropriate safety monitoring.
Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular events. Adverse event reports and vital signs will be collected at each study visit. 
The cardiovascular monitoring plan includes the following:

Regular monitoring of lipid levels

Potential MACE (cardiovascular death, myocardial infarction, stroke), other 
cardiovascular events (such as hospitalization for unstable angina, hospitalization for 
heart failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary 
interventions), VTE (DVT/PE), arterial thromboembolic events and noncardiovascular 
deaths will be identified by the investigative site or through medical review and will be 
sent to a blinded Clinical Event Committee for adjudication at regular intervals.
9.4.10.1. Venous Thromboembolic Event Assessment
If a patient develops clinical features of a DVT or PE, appropriate local laboratory tests and 
imaging should be performed, as necessary, for the diagnosis of the event.  For confirmed cases, 
additional laboratory testing is recommended as outlined in Appendix 5.  All suspected VTEs
will be independently adjudicated by a blinded Clinical Event Committee.
9.5.
Pharmacokinetics
A single venous blood sample will be drawn at the times indicated in the Schedule of Activities 
(Section 2).  These blood samples will be used to determine the plasma concentrations of 
baricitinib using a validated liquid chromatography tandem mass spectrometry method.  Blood 
samples that will be used for other laboratory assessments (for example, chemistry, hematology) 
may be drawn at approximately the same time as the samples drawn to determine plasma 

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concentrations of baricitinib, with the exception of Visit 2 (Week 0), which requires separate 
sampling from other labs.  The timing will be as follows:

At Visit 2 (Week 0), patients will take their investigational product in the clinic, and PK 
samples will be drawn approximately 15 minutes and 1 hour postdose.  Samples for the other 
clinical laboratory assessments must be drawn prior to receiving the first dose.

At Visit 4 (Week 4), patients will be asked to take their investigational product at home prior 
to visiting the clinic.  The clinic visit should be scheduled so that the blood sample collected
during this visit is drawn 2 to 4 hours after the dose is taken at home.

At Visit 5 (Week 8), patients will be asked to take their investigational product at home prior 
to visiting the clinic.  The clinic visit should be scheduled so that the blood sample collected
during this visit is drawn 4 to 6 hours after the dose is taken at home.

For Visit 6 (Week 12), and Visit 7 (Week 16), patients will take their investigational product
in the clinic, and a blood sample will be collected at any time predose on the day of the clinic 
visits.  If the patient has taken the oral dose prior to the visit, the sample may be drawn 
anytime postdose, and the inability to collect a predose sample will not be considered a 
protocol violation.

For an early termination visit prior to Visit 7 (Week 16), a sample may be drawn anytime if 
the last dose of investigational product was taken within the last 48 hours. If the early 
termination is due to an AE, then a sample should be drawn if the visit occurred prior to Visit 
16 (Week 52).  

In the event of an SAE, up to 2 additional blood samples may be taken at the investigator’s 
discretion.  If collected, the PK samples should be collected after the reported event, 
approximately 6 hours apart and within 24 hours of the patient’s last dose.
For visits where PK samples will be collected, the actual date and 24-hour clock time of sample 
collection, and the date and 24-hour clock time of the 2 doses prior to the sample being drawn, 
should be recorded.  For Visits 4 and 5, these 2 doses should be the dose taken the morning of 
the day of sample collection and the dose taken the day prior to sample collection.  For Visits 6 
and 7, these 2 doses should be the dose taken the day prior to sample collection and the dose 
taken 2 days prior to sample collection.
If the patient fails to follow the directions for a particular visit, the sample should still be 
collected at that visit, and the date and 24-hour clock time of sample collection and the date and 
24-hour clock time of the 2 doses prior to the sample being drawn should be recorded.
Pharmacokinetic samples will be kept in storage at a laboratory facility designated by the 
sponsor.  Pharmacokinetic samples may also be assayed for additional exploratory analyses.  
Pharmacokinetic results will not be provided to investigative sites until the completion of the 
study or to the blinded study team until the study has been unblinded.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.

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9.6.
Pharmacodynamics
Samples collected to measure pharmacodynamics markers including, but not limited to 
anti-dsDNA, complement, and IFN signature, will be identified by the patient number (coded) 
and retained at a facility selected by Lilly or its designee for a maximum of 1 year following last 
patient visit for the study.
9.7.
Pharmacogenomics
9.7.1. Whole Blood Samples for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis as specified in the 
Schedule of Activities (Section 2) where local regulations allow and patients provides consent.  
Patients choosing not to provide consent for whole blood samples to be collected for 
pharmacogenetic research will still be eligible to participate in the study.
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to baricitinib and to 
investigate genetic variants thought to play a role in SLE.  Assessment of variable response may 
include evaluation of AEs or differences in efficacy.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and/or ethical 
review boards (ERBs)/ institutional review boards (IRBs) impose shorter time limits.  This 
retention period enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of 
baricitinib or after baricitinib become(s) commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, and candidate gene studies.  Regardless of 
technology utilized genotyping data generated will be used only for the specific research scope 
described in this section.
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, PD, mechanism of action, variability of patient response (including safety), and 
clinical outcome.  Sample collection is incorporated into clinical studies to enable examination of 
these questions through measurement of biomolecules including deoxyribonucleic acid (DNA), 
ribonucleic acid (RNA), proteins, lipids, and other cellular elements.
Serum, plasma, whole blood RNA, and urine samples for biomarker research will be collected at 
the times specified in the Schedule of Activities (Section 2) where local regulations allow.

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Samples will be used for research on the drug target, disease process, variable response to 
baricitinib, pathways associated with SLE, mechanism of action of baricitinib, and/or research 
method or in validating diagnostic tools or assay(s) related to SLE.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained at a facility selected by Lilly or its designee for a maximum 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and ERBs/IRBs 
impose shorter time limits.  This retention period enables use of new technologies, response to 
regulatory questions, and investigation of variable response that may not be observed until later 
in the development of baricitinib or after baricitinib become(s) commercially available.  Any 
samples remaining after 15 years will be destroyed.
9.9.
Medical Resource Utilization and Health Economics
Health Economics and Medical Resource Utilization parameters will not be evaluated in this 
study.

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10. Statistical Considerations
10.1. Sample Size Determination
Study JAIA will aim to enroll approximately 750 patients ≥18 years of age in a 1:1:1 ratio 
between baricitinib 4-mg, 2-mg, and placebo.  The proposed samples size will ensure >90% 
power to detect an absolute difference of 17% between a baricitinib treatment group and the 
placebo treatment group assuming a 40% placebo response rate for the primary endpoint using a 
2-sided α of 0.05.  The anticipated effect size represents a clinically relevant difference.
An additional 10% (75 patients) may be enrolled due to COVID-19 related trial impacts.
Sample size and power estimates were obtained from nQuery® Advisor 7.0 using the χ2 test of 
equal proportions.

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10.2. Populations for Analyses
For purposes of analysis, the following populations are defined as outlined in Table JAIA.5.
Table JAIA.5.
Analysis Populations
Population
Description
Modified Intent-to-Treat (mITT)
Population
All patients who are randomized and receive at least 1 dose of investigational
product will be included in the mITT population. The intention-to-treat 
principle remains preserved since the decision of whether or not to begin 
treatment could not be influenced by knowledge of the assigned treatment in this 
double-blind study.  Patients will be analyzed according to the investigational 
product to which they were randomized. Unless otherwise specified, the 
efficacy and health outcomes analyses will be conducted on the mITT 
population.
Safety Population
The safety population is defined as all randomized patients who receive at least
1 dose of investigational product and who did not discontinue from the study for
the reason ‘Lost to Follow-up’ at the first postbaseline visit. Patients will be
analyzed according to the investigational product to which they were
randomized.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee. A detailed 
SAP describing the statistical methodologies will be developed by Lilly or its designee.
Efficacy and safety analyses will be conducted on the mITT and safety populations, respectively,
as described in in Table JAIA.5.
All tests of treatment effects will be conducted at a 2-sided α level of 0.05, unless otherwise 
stated.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.  Complete details of the planned analyses will be documented in the SAP.
For all analyses, Week 52 is considered to be equivalent to Visit 16, even if the timing of Visit 
16 was not within the protocol defined window.
10.3.1.1. Analysis Methods
Treatment comparisons of categorical efficacy and health outcomes variables will be made using 
a logistic regression analysis with Firth correction (Firth 1993; Heinze and Schemper 2001).  
Baseline disease activity (total SLEDAI-2K <10; ≥10), baseline corticosteroid dose 
(<10 mg/day; ≥10 mg/day prednisone or equivalent), region, and treatment group will be 
explanatory variables in the model. The p-value and 95% (unless otherwise specified) 
confidence interval (CI) for the odds ratio from the logistic regression model will be used for 

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primary statistical inference. The difference in percentages and 95% CI of the difference in 
percentages using the Newcombe-Wilson method without continuity correction will be used for 
descriptive purposes, unless otherwise specified. Missing data will be imputed using 
nonresponder imputation (NRI), as described in Section 10.3.1.2.
The primary analyses for all continuous efficacy and health outcome variables will use a 
restricted maximum likelihood-based mixed model for repeated measures (MMRM) analysis. 
The model will include treatment, baseline disease activity (total SLEDAI-2K <10; ≥10), 
baseline corticosteroid dose (<10 mg/day; ≥10 mg/day prednisone or equivalent), region, visit, 
treatment-by-visit interaction as fixed categorical effects, and baseline value and baseline 
value-by-visit interaction as fixed continuous effects to estimate change from baseline across 
postbaseline visits. The following covariance structures will be used to model the between- and 
within-patient errors: unstructured, heterogeneous Toeplitz, heterogeneous autoregressive, 
autoregressive (1), and heterogeneous compound symmetry.  The variance-covariance structure 
that results in the smallest Akaike information criterion (AIC) will be used.  The Kenward-Roger 
method will be used to estimate the denominator degrees of freedom. Type III tests for the 
least-squares (LS) means will be used for the statistical comparisons. The LS mean difference, 
standard error, p-value, and CIs will also be reported. Treatment group comparisons at specific 
study visits will be tested using the t-test obtained from the MMRM results.  Additional details 
of the MMRM method are described in Section 10.3.1.2.
Treatment comparisons of continuous efficacy and health outcome variables may also be made 
using analysis of covariance (ANCOVA).  This method may be used when no repeated measures 
are collected (e.g., SLICC/ACR), or as a sensitivity method to MMRM. Treatment, baseline 
disease activity (total SLEDAI-2K at screening <10; ≥10), baseline corticosteroid dose 
(<10 mg/day; ≥10 mg/day prednisone or equivalent), region, and baseline value will be included 
in the model. Type III tests for LS means will be used for statistical comparison between 
treatment groups. The LS mean difference, standard error, p-value, and 95% CI may also be 
reported. Any methods used to handle missing data will be specified in the SAP.
Time to first flare will be analyzed using a Cox proportional hazards model with treatment 
group, baseline disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), baseline corticosteroid 
dose (<10 mg/day; ≥10 mg/day prednisone or equivalent), and region fitted as explanatory 
variables.  Hazard ratios, 95% CI and p-values will be presented for treatment comparisons to 
placebo.  Patients who discontinue treatment early will be censored at the time of last dose of the 
study drug.
Missing data for patients who have COVID-19-related issues (that are not related to an adverse 
event of COVID-19 infection) may be imputed using alternative method, based on consultation 
with regulatory bodies, as appropriate.  Specific imputation methodologies, for this subgroup of 
patients, will be detailed in the SAP prior to the primary endpoint database lock.
The Fisher exact test will be used for the AEs, discontinuations, and other categorical safety data 
for between-treatment group comparisons.  Continuous vital signs, body weight, and other 
continuous safety variables including laboratory variables will be analyzed by ANCOVA with 

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treatment and baseline value in the model.  Shift tables for select categorical safety analyses (for 
example, “high” or “low” laboratory results) will also be produced.
10.3.1.2. Missing Data Imputation
As with any clinical study, patient dropouts and consequently missing data are expected.
Patients who discontinue treatment, unless they withdraw consent, will be encouraged to remain 
in the study and follow the scheduled visits until the primary analysis time point at Week 52 to 
provide the efficacy and safety data needed.  While every effort will be made to reduce missing 
data, the missing data imputation methods described below will be used to provide a 
conservative approach for assessing efficacy endpoints when patients have missing data.
The following imputation rules will be used:

Nonresponder imputation (NRI): For analysis of categorical efficacy and health 
outcomes variables such as SRI-4, missing data will be imputed using an NRI method.  
Patients who discontinue treatment early, increase use of corticosteroids above the 
baseline dose other than the permitted burst, as defined in the SAP, or have initiation of 
or an increase above baseline dose in immunosuppressant or antimalarial treatment, as 
defined in the SAP, any time after baseline will be defined as nonresponders. In some 
circumstances, due to COVID-19 related logistical issues, patients may require reduction 
or discontinuation of concomitant medications such as antimalarials due to unavailability, 
or discontinuation of immunosuppressants due to local guidelines.  These patients may 
require initiation or increase in dose of other medications, such as steroids, to replace the 
discontinued medications.  These medication changes may not define patients as 
nonresponders.

Mixed-model repeated measure (MMRM):  For continuous variables, the primary analysis 
will be a MMRM analysis with a missing at random assumption for handling missing 
data.  This analysis takes into account both missingness of data and the correlation of the 
repeated measurements.  For patients who increase use of corticosteroids above the 
baseline dose other than the permitted burst, as defined in the SAP, or have initiation of 
or an increase above baseline dose in immunosuppressant or antimalarial treatment, as 
defined in the SAP, any time after baseline, any observed data after that visit will be 
excluded from the MMRM analysis.  Observed data after permanent discontinuation of 
investigational product will be analyzed as observed, with the exception of any data that 
occur after increase in use of corticosteroids above the baseline dose other than the 
permitted burst, or initiation of or an increase above baseline dose in immunosuppressant 
or antimalarial treatment. In some circumstances, due to COVID-19 related logistical 
issues, patients may require reduction or discontinuation of concomitant medications 
such as antimalarials due to unavailability, or discontinuation of immunosuppressants due 
to local guidelines.  These patients may require initiation or increase in dose of other 
medications, such as steroids, to replace the discontinued medications.  For these specific 
COVID-19 cases, data will be treated as observed.

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
Tipping point analysis:  Various “tipping point” analyses will be performed to evaluate 
the robustness of statistical analyses for different objectives/estimands to the assumptions 
about missing data mechanism. This will be implemented by multiple imputation with 
sensitivity parameters (deltas) quantifying the degree of departure from the missingness 
at random (MAR) assumption by gradually worsening imputed outcomes for patients 
treated with baricitinib and/or improving the imputed outcomes for patients treated with 
placebo. The tipping point is identified as the combination of delta values for baricitinib 
and placebo that leads to a loss of statistical significance when evaluating baricitinib 
relative to placebo. Additional details of the tipping point analysis will be provided in the 
SAP.
Missing data for patients who have COVID-19-related issues (that are not related to an adverse 
event of COVID-19 infection) may be imputed using alternative methods, based on consultation 
with regulatory bodies, as appropriate.  Specific imputation methodologies, for this subgroup of 
patients, will be detailed in the SAP prior to the primary endpoint database lock.
Sensitivity analyses that include all randomized patients, including patients who did not receive 
any dose of investigational product, will be performed on the primary and select secondary 
outcome measures, if appropriate.  Additional sensitivity analyses, including additional methods 
of handling missing data or analyzing the data, that may be required to satisfy regulatory needs 
will be specified in the SAP.
10.3.1.3. Multiple Comparisons/Multiplicity
Multiplicity-controlled analyses will be performed on the primary and major secondary 
endpoints in order to control the overall family-wise Type I error rate at a 2-sided α level of 0.05. 
The graphical multiple testing procedure described in Bretz et al. (2011) will be used. The 
graphical approach is a closed testing procedure; hence, it strongly controls the familywise error 
rate across all endpoints (Alosh et al. 2014).  Details of the graphical testing scheme (including 
testing order, interrelationships, Type I error allocation, and the associated propagation) are 
included below (see Figure JAIA.2).  The final graphical testing scheme will be prespecified in 
the SAP.
The following is a list of primary and major secondary objectives to be tested:

Primary: Proportion of patients treated with baricitinib 4-mg QD compared to placebo 
achieving SRI-4 response at Week 52.

Major Secondary:

Proportion of patients treated with baricitinib 4-mg QD compared to placebo 
achieving an SRI-4 response at Week 24.

Proportion of patients treated with baricitinib 4-mg QD compared to placebo 
receiving >7.5 mg prednisone (or equivalent) at baseline able to decrease dose by 
≥25% to a prednisone equivalent dose of ≤7.5 mg/day maintained between 
Week 40 and Week 52.

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
Time to first severe flare (through Week 52) for patients treated with baricitinib 
4-mg QD compared to placebo.

Proportion of patients treated with baricitinib 4-mg QD compared to placebo 
achieving an LLDAS response at Week 52.

Change from baseline in Worst Pain NRS at Week 52 for patients treated with 
baricitinib 4-mg QD compared to placebo 

Change from baseline in FACIT-Fatigue at Week 52 for patients treated with 
baricitinib 4-mg QD compared to placebo

Proportion of patients treated with baricitinib 2-mg QD compared to placebo 
achieving an SRI-4 response at Week 52.

Proportion of patients treated with baricitinib 2-mg QD compared to placebo 
achieving an SRI-4 response at Week 24.

Proportion of patients treated with baricitinib 2-mg QD compared to placebo 
receiving >7.5 mg prednisone (or equivalent) at baseline able to decrease dose by 
≥25% to a prednisone equivalent dose of ≤7.5 mg/day maintained between 
Week 40 and Week 52.

Time to first severe flare (through Week 52) for patients treated with baricitinib 
2-mg QD compared to placebo.

Proportion of patients treated with baricitinib 2-mg QD compared to placebo 
achieving an LLDAS response at Week 52.

Change from baseline in Worst Pain NRS at Week 52 for patients treated with 
baricitinib 2-mg QD compared to placebo 

Change from baseline in FACIT-Fatigue at Week 52 for patients treated with 
baricitinib 2-mg QD compared to placebo
The sequentially rejective, weighted Bonferroni multiple testing procedure is completely 
specified by the following graph (Figure JAIA.2).

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Abbreviations:  CFB = change from baseline; LLDAS = Lupus Low Disease Activity 
State; SRI-4 = System Lupus Erythematosus Responder Index-4; TTE = time to event; 
W = week
Note:  All tests are 4-mg compared to placebo unless otherwise specified.  Testing for 
baricitinib 2-mg (compared to placebo) will occur in the same order as those 
prespecified for the 4-mg dose if all previous objectives were met.
Figure JAIA.2.
Illustration of graphical multiple testing procedure with initial α 
allocation and weights.
SRI-4
w24
SRI-4
w52
0.5
Steroid
Sparing
w40-52
LLDAS
w52
TTE 
Severe
Flare
0.5
Worst Pain
w52 CFB
FACIT-F
w52 CFB
2mg
SRI-4 
w52
1.0
α=0.05

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The primary objective will first be tested at α = 0.05.  If the null hypothesis is not rejected, no 
further testing is conducted, as the α for that test is considered “spent” and cannot be passed to 
other endpoints.  If the null hypothesis is rejected, all α will be propagated to the next 
objective(s).  The testing process continues, with α propagated according to the weights on the 
corresponding edges displayed in Figure JAIA.2, as long as there is at least one hypothesis that 
can be rejected at its allocated α level.  Each time a hypothesis is rejected, the graph is updated to 
reflect the reallocation of α, which is considered “recycled” by Alosh et al. (2014).  This iterative 
process of updating the graph and reallocating α is repeated until all hypotheses have been tested 
or when no remaining hypotheses can be rejected at their corresponding α levels.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
A detailed description of patient disposition by treatment will be summarized with reasons for 
discontinuation.  Frequency counts and percentages will be presented for each treatment group.  
All patients who discontinue from the study will be identified, and the extent of their 
participation in the study will be reported along with their reason for discontinuation.
10.3.2.2. Patient Characteristics
Demographic and baseline characteristics will be summarized descriptively by treatment group. 
Descriptive statistics including number of patients, mean, standard deviation, median, minimum, 
and maximum will be provided for continuous measures, and frequency counts and percentages 
will be tabulated for categorical measures. No formal statistical comparisons will be made 
among treatment groups unless otherwise stated.  A complete list of patient characteristics and 
baseline clinical measures will be provided in the SAP.
10.3.2.3. Concomitant Therapy
Concomitant medications will be coded and descriptively summarized by treatment group in 
terms of frequencies and percentages using the safety population. 
10.3.2.4. Treatment Compliance
Compliance with investigational product treatment for baricitinib and placebo will be assessed 
through counts of returned investigational product tablets.  A patient will be considered 
significantly noncompliant if he or she misses more than 20% of the prescribed doses during the 
study, that is, compliance <80%. Similarly, a patient will be considered significantly 
noncompliant if he or she is judged by the investigator to have intentionally or repeatedly taken 
more than the prescribed amount of medication.
10.3.3. Efficacy Analyses
10.3.3.1. Primary Analyses
The primary efficacy measure is SRI-4 response (defined in Section 9.1.1).  A logistic regression 
model with Firth correction (as described in Section 10.3.1.1) will be used to test the treatment 
difference between baricitinib 4-mg and placebo in the proportion of patients achieving SRI-4
response at Week 52.  Missing data will be imputed using the NRI method described in

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Section 10.3.1.2.  Missing data for patients who have COVID-19-related issues (that are not 
related to an adverse event of COVID-19 infection) may be imputed using alternative method, 
based on consultation with regulatory bodies, as appropriate.  Specific imputation 
methodologies, for this subgroup of patients, will be detailed in the SAP prior to the primary 
endpoint database lock.
10.3.3.2. Major Secondary Analyses
The major secondary comparisons will be based on the multiple testing procedure detailed in 
Section 10.3.1.3.
Treatment comparisons in the proportion of patients achieving a binary response will be 
analyzed using logistic regression with Firth correction.  Treatment comparisons in the 
continuous measures will be analyzed using MMRM.  Treatment comparisons for time to first 
flare will be analyzed using a Cox proportional hazards model.  These methods are described in 
Section 10.3.1.1.  Missing data for the binary outcome measures will be imputed using the NRI 
method described in Section 10.3.1.2.  Missing data for patients who have COVID-19-related 
issues (that are not related to an adverse event of COVID-19 infection) may be imputed using 
alternative method, based on consultation with regulatory bodies as appropriate.  Specific 
imputation methodologies, for this subgroup of patients, will be detailed in the SAP prior to the 
primary endpoint database lock.
10.3.3.3. Other Secondary and Exploratory Analyses
There will be no adjustment for multiple comparisons.  Analyses will be conducted for the other 
secondary and exploratory objectives, which include health outcomes, defined in Section 9.1.1. 
The analysis methods will generally follow those specified in Section 10.3.1.1. Specific details 
of analyses will be specified in the SAP.
10.3.4. Safety Analyses
All safety data will be summarized by treatment group and analyzed using the safety population.  
Safety assessments will include AEs, laboratory analytes, vital signs, and questionnaires to 
assess the existence and severity of depression.  Analyses will focus on comparisons of 
baricitinib to placebo, using the safety analysis methods described in Section 10.3.1.1.
10.3.4.1. Adverse Events
Adverse events are classified based upon the Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment-emergent adverse events are defined as AEs that first occurred or 
worsened in severity on or after the date of the first dose of investigational product. The number 
of TEAEs as well as the number and percentage of patients who experienced at least 1 TEAE 
will be summarized using MedDRA for each system organ class (or a body system) and each 
preferred term by treatment group. For events that are gender-specific, the denominator and 
computation of the percentage will only include patients from the given gender.
Serious adverse events (including deaths), treatment-emergent AESIs, and AEs that lead to 
investigational product discontinuation or interruption will also be summarized using MedDRA 
for each system organ class and each preferred term by treatment group.  Potential AESIs will be 

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identified by a standardized MedDRA query or a Lilly-defined MedDRA query.  Details of the 
AESIs (listed in Section 9.2.2) and other events of interest and analysis methods will be 
documented in the SAP or program safety analysis plan. 
10.3.4.2. Clinical Laboratory Tests
All clinical laboratory results will be descriptively summarized by treatment group.  Individual 
results that are outside the normal reference ranges will be flagged in data listings.  Quantitative 
clinical hematology, chemistry, and urinalysis variables obtained at the baseline to postbaseline 
visits will be summarized as changes from baseline.  Categorical variables, including the 
incidence of abnormal values and incidence of AESIs, will be summarized by frequency and 
percentage of patients in corresponding categories.  Shift tables will be presented for selected 
measures.
10.3.4.3. Vital Signs, Physical Findings, and Other Safety Evaluation
Observed values and changes from baseline (predose or screening if missing) for vital signs and 
physical characteristics, and other continuous safety measures will be descriptively summarized 
by treatment group and time point.  Shift tables will be presented where appropriate.
Summary tables or listings for the C-SSRS and the Self-Harm Supplement Form will be 
produced as needed.
The incidence, duration, and reasons of investigational product interruptions will be summarized 
and compared descriptively among treatment groups.
Further analyses may be performed and will be planned in the SAP.
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
All plasma baricitinib concentration-time data will be pooled and evaluated using population PK 
methods.  A covariate screen of patient and study-specific factors will be included in the analyses 
based on factors investigated in previous and (if any) ongoing PK analyses, and on their 
relevance to the target population.  Exploratory and/or model-based analyses examining the 
relationships between baricitinib exposure and efficacy and response endpoints will be 
conducted.  Other analyses of efficacy and safety outcome measures may also be assessed as 
scientifically appropriate and warranted by available data.  Details about the analyses to be 
conducted will be contained in the PK/PD analysis plan.
10.3.6. Interim Analyses
A data monitoring committee (DMC) will oversee the conduct of all the Phase 3 clinical trials 
evaluating baricitinib in patients with SLE.  The DMC will consist of members external to Lilly.  
This DMC will follow the rules defined in the DMC charter, focusing on potential and identified 
risks for this molecule and for this class of compounds.  Data monitoring committee membership 
will include, at a minimum, specialists with expertise in rheumatology, statistics, and other 
appropriate specialties.  This DMC for studies of patients with SLE may be coordinated with the 
DMC(s) for other ongoing studies of baricitinib in other indications. Details of the DMC will be 
documented in a DMC charter.

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Access to the unblinded data will be limited to the DMC and statisticians providing the data.  
These statisticians will be independent from the study team.  The study team will not have access 
to the unblinded data.  Only the DMC is authorized to evaluate unblinded interim efficacy and 
safety analyses. The study sites will receive information about interim results ONLY if they need 
to know for the safety of their patients.  The DMC may request to review efficacy data to 
investigate the benefit/risk relationship in the context of safety observations for ongoing patients 
in the study.  
In addition to the planned safety-related interim analyses, interim efficacy analyses may be 
conducted prior to completion of the study.  Using predefined thresholds, the trial may be 
stopped if the probability of the trial meeting its primary efficacy endpoint falls below an 
acceptable level.  The DMC charter will describe the precise decision guidelines governing the 
interim analyses.  The trial will not be stopped for positive efficacy; therefore, no alpha 
adjustment is needed.
In addition to the DMC members, a limited number of pre-identified individuals may gain access 
to the limited unblinded data, as specified in the unblinding plan, prior to the final database lock, 
in order to initiate the population PK/PD model development processes.  These analyses will not 
be considered interim analyses.  Information that may unblind the study during the analyses will 
not be reported to study sites or blinded study team until the study has been unblinded.

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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
ACR
American College of Rheumatology
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
AESI
Adverse events of special interest
AGS
Aicardi-Goutières Syndrome
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANA
antinuclear antibody
ANC
absolute neutrophil count
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
BILAG
British Isles Lupus Assessment Group
blinding/masking
A double-blind study is one in which neither the [patient/subject] nor any of the 
investigator or sponsor staff who are involved in the treatment or clinical evaluation of 
the subjects are aware of the treatment received.
CANDLE
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature
BPI
Brief Pain Inventory
CFR
Code of Federal Regulations
CI
confidence interval
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CNS
central nervous system
CIOMS
Council for International Organizations of Medical Sciences
Companion diagnostic
An in vitro diagnostic device (assay or test) that provides information that is essential for 
the safe and effective use of a corresponding therapeutic product

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complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
CRP
clinical research physician: Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research scientist, 
global safety physician or other medical officer.
CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
COVID-19
coronavirus disease
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DSM-V
Diagnostic and Statistical Manual of Mental Disorders
DVT
deep vein thrombosis
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
eCOA
electronic clinical outcome assessment
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the trial are 
those who have been assigned to a treatment.
enter
Patients entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
ePRO
electronic patient reported outcome
ERB
ethics review board
FACIT
Functional Assessment of Chronic Illness Therapy-Fatigue
GCP
good clinical practice
GPS
Global Patient Safety
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus

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HCV
hepatitis C virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IFN
interferon
Ig
immunoglobulin
IL
interleukin
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
IL
interleukin
investigational product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB
institutional review board
ITT
intention to treat: The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a patient (that is, the 
planned treatment regimen) rather than the actual treatment given.  It has the 
consequence that patients allocated to a treatment group should be followed up, assessed,
and analyzed as members of that group irrespective of their compliance to the planned 
course of treatment.
IUD
intrauterine device
IVRS/IWRS
interactive voice-response system/interactive web-response system
JAK
Janus kinase
JDM
juvenile dermatomyositis
LLDAS
Lupus low disease activity state
LS
least squares
LTE
long-term extension
MACE
major adverse cardiovascular events
MCS
mental component score
MDRD
Modification of Diet in Renal Disease

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MedDRA
Medical Dictionary for Regulatory Activities
MI
myocardial infarction
mITT
modified intent-to-treat population
MMRM
mixed model for repeated measures
MTX
methotrexate
NRI
nonresponder imputation
NRS
Numeric Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
PCS
physical component score
PE
pulmonary embolism
PK/PD
pharmacokinetics/pharmacodynamics
PPD
purified protein derivative
PPS
per-protocol set: The set of data generated by the subset of patients who sufficiently 
complied with the protocol to ensure that these data would be likely to exhibit the effects 
of treatment, according to the underlying scientific model.
PRO
patient-reported outcomes
PSAP
program safety analysis plan
QD
once daily
QIDS-SR16
Quick Inventory of Depressive Symptomatology
QTc
corrected QT interval
RA
rheumatoid arthritis
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SAVI
Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset During 
Infancy
screen
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical study. 
SF-36v2
Short-Form 36-item Health Survey version 2

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SFI
SELENA-SLEDAI Flare Index
SLE
systemic lupus erythematosus
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SLICC
Systemic Lupus Erythematosus International Collaborating Clinics
SoC
Standard of care
SRI-4
Systemic Lupus Erythematosus Responder Index-4
STAT
signal transducers and activators of transcription
SUSARs
suspected unexpected serious adverse reactions
TB
tuberculosis
TBL
total bilirubin level
TEAE
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, which and does not necessarily have to have a causal 
relationship with this treatment.
TSH
thyroid-stimulating hormone
TYK
tyrosine kinase
ULN
upper limit of normal
VAS
Visual Analog Scale
VTE
venous thromboembolic event
WPAI-Lupus
Work Productivity and Activity Impairment-Lupus

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Appendix 2.
Clinical Laboratory Tests
Clinical Laboratory Testsa
Hematologyb
Clinical Chemistryb
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Absolute reticulocyte count
Total bilirubin
Mean cell volume (MCV)
Direct bilirubin
Mean platelet volume
Alkaline phosphatase (ALP)
Mean cell hemoglobin (MCH)
Mean cell hemoglobin concentration (MCHC)
Alanine aminotransaminase (ALT)/serum glutamic pyruvic 
transaminase
Leukocytes (WBC)
Absolute count of
Aspartate aminotransferase (AST)/serum glutamic oxaloacetic 
transaminase 
Neutrophils, segmented
Blood urea nitrogen (BUN)
Neutrophils, juvenile (bands)
Creatinine
Lymphocytes
Estimated glomerular filtration rate (eGFR)c
Monocytes
Uric acid
Eosinophils
Calcium
Basophils
Glucosed
Platelets
Albumin
Cell morphology
Creatine phosphokinase (CPK)
Differential and blood smeare
Total protein
Iron studies (iron, TIBC, and ferritin)
Lymphocyte subsets (T, B, NK, and T cell 
subsets)
Lipid Profiled,f
Urinalysisb,n
Total cholesterol
Color
High-density lipoprotein cholesterol (HDL-C)
Specific gravity
Low-density lipoprotein cholesterol (LDL-C)
pH
Triglycerides 
Urine Protein
Glucose
Other Tests
Ketones
Serum pregnancy test (females only)g
Blood
Urine pregnancy test (females only)g
Bilirubin
Follicle-stimulating hormone (FSH) (females only)h
Urobilinogen
Hepatitis B surface antigen (HBsAg)
Leukocyte esterase
Hepatitis B surface antibody (HBsAb)
Nitrite
Hepatitis B core antibody (HBcAb), total
Microscopic examination of sedimentj
Hepatitis C antibodyi
Urine creatinine
HBV DNAk
Urine protein
HCV RNAi
Urine protein-creatinine ratio
Human immunodeficiency virus (HIV) serology
PPD or QuantiFERON®-TB Gold, or T-SPOT®.TBl
Thyroid-stimulating hormone (TSH)

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Abbreviations:  dRVVT = Dilute Russell’s Viper Venom Time; dsDNA = double-stranded deoxyribonucleic acid;
HBV DNA = hepatitis B virus deoxyribonucleic acid; HCV RNA = hepatitis C virus ribonucleic acid;
Ig = immunoglobulin; mRNA = messenger ribonucleic acid; PK = pharmacokinetics; PPD = purified protein 
derivative; RBC = red blood cells; TIBC = total iron binding capacity; WBC = white blood cells.
a
All labs will be assayed/calculated by a Lilly-designated laboratory unless otherwise noted.
b
Unscheduled blood chemistry hematology, and urinalysis panels may be performed at the discretion of the 
investigator.
c
eGFR for serum creatinine will be calculated by the central laboratory using the Modification of Diet in Renal 
Disease (MDRD) isotope dilution mass spectrometry traceable method.
d
Fasting laboratory values for glucose and lipids will be required at baseline, Weeks 12, 24, 36, and 52. Patients 
should not eat or drink anything except water for 12 hours prior to test. If a patient attends these visits in a 
nonfasting state, this will not be considered a protocol violation.
e
Differential and blood smear may be performed if necessary.
f
Lipid panel consists of direct HDL-C, triglycerides, cholesterol, and LDL-C (calculation from Friedewald et al. 
1972).
g
For all women of child-bearing potential, a serum pregnancy test (central laboratory) will be performed at 
Visit 1. Urine pregnancy tests (local laboratory) will also be performed at each subsequent study visit per the 
Schedule of Activities.
h
For female patients ≥50 and <55 years of age who have had a cessation of menses for at least 6 and less than 12 
months, an FSH test will be performed to confirm non-child-bearing potential (FSH ≥40 mIU/mL).
i
A confirmatory test of HCV RNA will be performed if the patient is positive for HCV antibody.
j
Microscopic examination of sediment will be performed if abnormalities are noted on the routine urinalysis.
k
HBV DNA testing will be performed in patients who tested positive for HBcAb at screening.
l
In countries where the QuantiFERON®-TB Gold test or T-SPOT® is available, either test may be used instead of 
the PPD TB test.  The QuantiFERON®-TB Gold test must be performed centrally; the T-SPOT® must be 
performed locally. See Exclusion Criterion [29] for details.
m Interferon signature may be assayed from stored mRNA sample.
n
Urine should be collected as a clean catch sample.
Autoantibodies
Serum immunoglobulins (IgG, IgA, IgM)
Anti-nuclear antibody (ANA)
Stored serum, plasma, urine, mRNAm, and DNA samples for 
exploratory biomarker analyses
Anti-double-stranded DNA (anti-dsDNA) 
antibody
Baricitinib plasma concentration (PK sample)
Anti-Smith
Lupus anticoagulant (dRVVT)
Autoantibodies (anti-RNP, anti-Sm, 
anti-SSA/Ro, anti-SSB/La)
Complement C3 and C4
Anti-cardiolipin antibodies IgG, IgA, IgM
Anti-beta2 glycoprotein-I (IgG, IgM)

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Appendix 3. Study Governance Considerations

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Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1.
Informed Consent
The investigator is responsible for:

ensuring that the patient understands the nature of the study, the potential 
risks and benefits of participating in the study, and that their participation is 
voluntary.

ensuring that informed consent is given by each patient or legal 
representative.  This includes obtaining the appropriate signatures and dates 
on the informed consent form (ICF) prior to the performance of any protocol 
procedures and prior to the administration of investigational product.

answering any questions the patient may have throughout the study and 
sharing in a timely manner any new information that may be relevant to the 
patient’s willingness to continue his or her participation in the study.

ensuring that a copy of the ICF is provided to the participant or the 
participant’s legal representative and is kept on file.

ensuring that the medical record includes a statement that written informed 
consent was obtained before the participant was enrolled in the study and the 
date the written consent was obtained.  The authorized person obtaining the 
informed consent must also sign the ICF.
Appendix 3.1.2.
Recruitment
Lilly or its designee is responsible for the central recruitment strategy for patients.  Individual 
investigators may have additional local requirements or processes.
Appendix 3.1.3.
Ethical Review
The investigator or an appropriate local representative must give assurance that the ethical 
review board (ERB) was properly constituted and convened as required by International Council 
for Harmonisation (ICH) guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s).  All ICFs 
must be compliant with the ICH guideline on Good Clinical Practice (GCP).
The study site’s ERB(s) should be provided with the following:

the protocol and related amendments and addenda, current Investigator 
Brochure (IB) and updates during the course of the study

informed consent form

Other relevant documents (for example, curricula vitae, advertisements)

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Appendix 3.1.4.
Regulatory Considerations
This study will be conducted in accordance with the protocol and with the following:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of
Medical Sciences (CIOMS) International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third party.
Appendix 3.1.5.
Investigator Information
Physicians with a specialty in rheumatology will participate as investigators in this clinical trial.
Physicians with other specialties and experience in treatment of patients with systemic lupus 
erythematosus (SLE) may also participate as investigators.
Appendix 3.1.6.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.7.
Final Report Signature
The clinical study report (CSR) coordinating investigator will sign the final CSR for this study, 
indicating agreement that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
The sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 3.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

sponsor start-up training to instruct the investigators and study coordinators.  This
training will give instruction on the protocol, the completion of the CRFs, and 
study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax

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
review and evaluate CRF data and use standard computer edits to detect errors in 
data collection

conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1.
Data Capture System
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site into the sponsor-provided electronic data capture system.
Electronic patient-reported outcome (ePRO) measures (e.g., a rating scale) and electronic clinical 
outcome assessments (eCOAs) are entered into an ePRO/eCOA instrument at the time that the 
information is obtained.  In these instances where there is no prior written or electronic source 
data at the site, the ePRO/eCOA instrument record will serve as the source.
If ePRO/eCOA records are stored at a third party site, investigator sites will have continuous 
access to the source documents during the study and will receive an archival copy at the end of 
the study for retention.
Any data for which the ePRO/eCOA data record will serve as source data will documented by 
the site in their study file.
Case report form data collected by a third-party will be encoded by the third-party and stored 
electronically in the third-party’s database system.  Validated data will subsequently be 
transferred to the sponsor’s data warehouse, using standard Lilly file transfer processes.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse. 
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

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Appendix 3.3.
Study and Site Closure
Appendix 3.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.
Appendix 3.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
The publication policy for Study I4V-MC-JAIA is described in the Clinical Trial Agreement.

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Appendix 4.
Hepatic Monitoring Tests for 
Treatment-Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly, or its designee, clinical 
research physician.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Alkaline Phosphatase Isoenzymesa
CPK
Anti-smooth muscle antibody (or anti-actin antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspirate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalized 
ratio; RBC = red blood cells; WBC = white blood cells.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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Appendix 5.
Monitoring Tests for Confirmed VTE
Selected tests may be obtained in the event of a confirmed venous thromboembolic event (VTE)
and may be required in follow-up with patients in consultation with Eli Lilly and Company, its 
designee, or the Lilly designated medical monitor.  The choice and optimal timing of these tests 
will be directed by the patient’s management and may require ongoing follow-up after study 
discontinuation.
Protein C Functional
Protein S Clottable
Antithrombin III
APC Resistance
PT
APTT
Fibrinogen
Cardiolipin Antibodies
PT Gene
Factor VIII C Assay
Hexagonal Phase Phospholipid Neutralization
C-Reactive Protein
PTT Incubated Mixing 
Dilute Russell Viper Venom 
Platelet Neutralization 
Factor V Leiden 
MTHFR 
Thrombin Time 
Reptilase 
Fibrinogen Antigen 
Protein C Immunologic 
Protein S Immunologic 
Heparin fXa Inhibition 
Abbreviations:  APC = activated protein C; APTT = activated partial thromboplastin time; MTHFR = methylene 
tetrahydrofolate reductase; PT = prothrombin time; PTT = partial thromboplastin time.

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Appendix 6.
Protocol Amendment I4V-MC-JAIA(b) 
Summary - A Randomized, Double-Blind, 
Placebo-Controlled, Parallel-Group, Phase 3 Study of 
Baricitinib in Patients with Systemic Lupus Erythematosus
Overview
Protocol I4V-MC-JAIA, A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 
Phase 3 Study of Baricitinib in Patients with Systemic Lupus Erythematosus, has been amended.  
The new protocol is indicated by amendment (b) and will be used to conduct the study in place 
of any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are described in the 
following table. Editorial revisions with no impact on protocol design or implementation were 
also made.  These revisions are not noted in this protocol amendment summary except where
contained in a section with substantive changes.

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Amendment Summary for Protocol I4V-MC-JAIA Amendment (b)
Section # and Name
Description of Change
Brief Rationale
Section 1 – Synopsis Objectives and Endpoints
Section 4 - Objectives and Endpoints
Section 9.1.1 – Primary Efficacy Assessment 
SRI-4 response definition clarified by replacing 
“or” with “and” in the following: “no new BILAG 
A and no more than 1 new BILAG B disease 
activity score
Updated to correct a typographical error
Section 1 – Synopsis Number of Patients and 
Statistical Analysis
Section 10.1 – Sample Size Determination
Section 10.3.1.1 – Analysis Methods
Section 10.3.1.2 – Missing Data Imputation
Section 10.3.3.1 – Primary Efficacy Assessment
Section 10.3.3.2 – Major Secondary Analyses
Added the possibility of enrolling 75 more patients 
and added an explanation of how missing data for 
COVID-19 impacted patients will be imputed.
Updated patient number and statistical analysis to 
account for COVID-19 affected patients.
Section 1 – Synopsis Treatment Arms and Duration
Section 2 – Schedule of Activities
Section 5.1 – Overall Design
Section 7.8.1 – Study Extensions
Section 10.3.1 - General Statistical Considerations
Section 10.3.1.2 – Missing Data Imputation
To mitigate COVID-19 related logistical issues and 
impact on analyses:

Added potential for patients who were unable 
to complete Visit 16 in the protocol specified 
timeframe to participate in Study JAIM.

Added potential for delaying Visit 16 and 
dispensing additional IP.

Added clarification that Week 52 is considered 
to be equivalent to Visit 16, even if the timing 
of Visit 16 was not within the protocol defined 
window.

Added considerations for COVID-19 related 
concomitant medication changes in relation to 
missing data imputation.
Updated protocol to include provisions put into 
place in order to assure the safety of trial 
participants and minimizing risks to trial integrity 
during the COVID-19 pandemic.
Section 2 - Schedule of Activities 
Added “and” to clarify that the C-SSRS and Self-
Clarified that both the C-SSRS and Self-Harm 

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Section # and Name
Description of Change
Brief Rationale
Harm Supplemental Form are separate scales and 
both require completion at the indicated visits. The 
footnote was updated to include both the C-SSRS 
and the Self-Harm Supplement Form.
Supplemental Form are required to reduce risk for 
missing data.
Section 4 – Objectives and Endpoints
Section 9.1.2.10 – British Isles Lupus Assessment 
Group Based Composite Lupus Assessment
Subsection added to add BICLA as other secondary 
(non-multiplicity controlled) endpoint, and included 
a description of the assessment.
Analysis of BICLA endpoint was included in the 
protocol to supplement efficacy analyses.
Section 6.1 – Inclusion Criteria
Hormonal contraception dosage forms were 
corrected from oral, intravaginal, or transdermal to 
oral, injectable, or implantable.
Updated to correct a typographical error
Section 6.2 – Exclusion Criteria
Exclusion criterion 18, which excludes patients 
with a history of recurrent (≥ 2) VTEs, was revised 
to include “(DVT/PE)” as a clarifier.
Exclusion criterion 32, which excludes patients 
who have received a JAK inhibitor, was updated to 
specify that those who have received a TYK-2 
inhibitor are also excluded.
Updated for consistency.
Updated to clarify that patients who have received a 
TYK-2 inhibitor are excluded, given that TYK-2 
inhibitors may act on the similar mechanisms as 
JAK inhibitors.
Section 6.4 – Screen Failure
Text was changed from “The interval between 
initial screen failure and rescreening Visit 1…” to 
“The interval between initial screening and 
rescreening Visit 1.”
Updated to correct a typographical error.
Section 7.7. - Concomitant Therapy
Added statement to clarify that reductions in dose
of treatments for SLE or other concurrent illnesses 
for safety reasons are permitted per protocol.
In Section 7.7.2, added “for SLE” to the conditions 
under which patients who require prohibited 
corticosteroid doses will be discontinued from 
study drug.
Updated to clarify that while most concomitant 
medications should remain stable during the trial, 
reductions in dose for safety are permitted.
Updated to clarify that prohibited use of 
corticosteroids for SLE requires discontinuation 
from study drug, while use of prohibited doses of 
corticosteroids for other reasons may not require 

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Section # and Name
Description of Change
Brief Rationale
In Section 7.7.2, added “as defined in the SAP” to 
descriptions of prohibited changes in concomitant 
therapy.
discontinuation of study drug. 
Clarified that definitions of increases in 
corticosteroids, antimalarials, and 
immunosuppressants are further detailed in the 
SAP.
Section 9.4.10.1 – Venous Thromboembolic Event 
Assessment
Text was changed from “All suspected VTE events 
will be independently adjudicated…” to “All 
suspected VTEs will be independently 
adjudicated…”.
Updated to correct a typographical error.
Section 10.3.1.2 – Missing Data Imputation
Added “as defined in the SAP” to NRI and MMRM 
descriptions.
Clarified that increases in corticosteroids, 
antimalarials, and immunosuppressants that trigger 
missing data imputation are futher detailed in the 
SAP.
Section 10.3.6 – Interim Analyses
Text outlining an interim analysis was added.
Text that indicated that there is no planned futility 
assessment and that an adjustment to type I error 
would be made if an unplanned futility analysis for 
efficacy is performed, was removed.
An interim analysis has been added to assess the 
likelihood of trial failure time prior to trial 
conclusion in order to minimize patient exposure to 
an ineffective drug. Because an interim analysis to 
assess inadequate efficacy has been added, the text 
about ‘no planned futility assessment’ was 
removed.

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.

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1.
Synopsis and Table JAIA.1.
…
Objective(s)/Endpoints:
Objectives
Endpoints
Primary
To evaluate the effect of baricitinib 4-mg QD and 
background standard-of-care (SoC) therapy compared 
to placebo and SoC on SLE disease activity.
Proportion of patients achieving an SRI-4 response at 
Week 52, defined as:

Reduction of ≥4 points from baseline in 
SLEDAI-2K score; and

No new British Isles Lupus Assessment Group 
(BILAG) A or and no more than 1 new BILAG B 
disease activity score; and

No worsening (defined as an increase of 
≥0.3 points [10 mm] from baseline) in the 
Physician’s Global Assessment of Disease 
Activity.
Treatment Arms and Duration
At Week 0, patients will be randomized to 1 of 3 treatment groups: placebo once daily (QD), 
baricitinib 2-mg QD, or baricitinib 4-mg QD. The study duration will be up to 62 weeks 
(Screening Period: up to 6 weeks prior to randomization; Double-Blinded Treatment Period: 
52 weeks; [In some circumstances, due to COVID-19 related logistical issues, Visit 16 may be 
completed outside of the protocol specified timeframe, thus the treatment period may be 
extended.  Where allowed locally, additional IP (typically not to exceed 1 extra month’s supply) 
may be dispensed to prevent interruption of study drug.]; Follow-up Period: approximately 4 
weeks after the last dose of investigational product.
Number of Patients:
The study will include approximately 750 patients with SLE who will be randomized 1:1:1 to 
receive placebo QD, baricitinib 2-mg QD, or baricitinib 4-mg QD (250 patients in each treatment 
group).  An additional 10% (75 patients) may be enrolled due to COVID-19 related trial impacts.
Statistical Analysis
…
Treatment comparisons of categorical efficacy and health outcomes variables will be made using 
a logistic regression analysis with Firth correction (Firth 1993; Heinze and Schemper 2001).  
Baseline disease activity, baseline corticosteroid dose, region, and treatment group will be 
explanatory variables in the model.  The p-value and 95% confidence interval (CI) for the odds 
ratio from the logistic regression model will be used for primary statistical inference.  Patients 
who discontinue treatment early, increased use of corticosteroids above the baseline dose other 
than the permitted burst, as defined in the SAP, or have initiation of or an increase above the 
baseline dose in immunosuppressant or antimalarial treatment any time after baseline, as defined 

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in the SAP, will be defined as nonresponders and the data will be imputed using the 
nonresponder imputation (NRI) method.
…
Missing data for patients who have COVID-19-related issues (that are not related to an adverse 
event of COVID-19 infection) may be imputed using alternative method, based on consultation 
with regulatory bodies, as appropriate.  Specific imputation methodologies, for this subgroup of 
patients, will be detailed in the SAP prior to the primary endpoint database lock.

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2.
Schedule of Activities
Table JAIA.1.
Schedule of Activities
Screening
Double-Blinded Treatment
Post-Treat
ment 
Follow-up
Visit Number
V1
V2a
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
V16b,c
ETdc
V801ed
Procedures and Assessments
Physical examinationfe
X
Symptom-directed 
physical examinationfe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BPgf, 
pulse, temperature)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Substance use 
(caffeine, alcohol, 
tobacco)
X
ECGhg
X
Administer TB testih
X
Read PPD test (if 
applicable)ji
X
Chest x-raykj
X
Confirm SLE 
Criterialk
X
C-SSRSml and 
Self-Harm Supplement 
Form
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up 
Formnm
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16
X
X
X
X
X
X
X
X
Randomizationon
Xon

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Log in IWRS
X
Xon
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigational product 
dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xc
Investigational product 
returned and 
compliance assessed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO (patient diary) 
dispensed/returnedpo,q
p
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xpo
Xpo
Xpo
Physician-Completed Scalesrq
Patient Questionnaires
Worst Pain NRSqp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Joint Pain 
NRSqp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Fatigue NRSqp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Joint Stiffness 
Durationqp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Joint Stiffness Severity 
NRSqp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Impression of Severity 
(PGI-S)qp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Impression of Change 
(PGI-C)sr
X
X
X
SF-36v2sr
X
X
X
X
X
X
FACIT-Fatiguesr
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
WPAI-Lupussr
X
X
X
X
X
X
X
EQ-5D-5Lsr
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
Hepatitis C virus 
(HCV) antibody 
testingts
X

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HBV DNAut
X
X
X
X
X
X
X
X
Serum pregnancy 
testvu
X
Urine pregnancy testvu
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
FSHwv
X
Clinical chemistryxw
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting lipid panelyx
X
X
X
X
X
Urinalysiszbb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Baricitinib plasma 
concentrations (PK 
sample)
Xaa
z
Xaa
z
Xaa
z
Xaa
z
Xaa
z
Xaa
z
Pharmacogenetic 
(DNA) collectionbbaa
X
X
X
Abbreviations:  ANA = antinuclear antibody; BILAG = British Isles Lupus Assessment Group; BP = blood pressure; CLASI = Cutaneous Lupus Erythematosus 
Disease Area and Severity Index; COVID-19 = coronavirus disease;

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b Patients who complete the treatment period through Visit 16 may be eligible to participate in the long-term extension study (I4V-MC-JAIM [JAIM]).  For 
patients enrolled in JAIM, Visit 1 of Study JAIM should occur on the same day as Visit 16 of Study I4V-MC-JAIA (JAIA).  In some circumstances, due to 
COVID-19 related logistical issues, patients who were unable to complete Visit 16 in the protocol specified timeframe and had study drug temporarily 
interrupted, but otherwise completed the treatment period, may be eligible to participate in Study JAIM.
c
In some circumstances, due to COVID-19 related logistical issues, Visit 16 may be completed outside of the protocol specified timeframe. Where allowed 
locally, additional investigation product (IP, typically not to exceed 1 extra month’s supply) may be dispensed to prevent interruption of study drug during the 
treatment period.
cd Those patients who discontinue from the study prior to Visit 16 should complete the ET visit and proceed to post-treatment follow-up.
de Patients should return for Visit 801, a post-treatment follow-up visit, 28±5 days after the last dose of investigational product.  Patients who complete the 
treatment period through Visit 16 and enter the long-term extension (LTE; JAIM) will not complete Visit 801 in Study JAIA, as they will complete 
post-treatment follow-up at the conclusion of JAIM. Patients who discontinue investigational product (IP) but remain in the study for at least 28±5 days 
without IP can combine their Visit 16/ET with their Visit 801 (post-treatment follow-up visit).
ef One complete physical examination (excluding pelvic and rectal examinations) will be performed at Visit 1.  All subsequent physical examinations may be 
symptom-directed.  A complete physical examination may be repeated at the investigator’s discretion any time.
fg At each time point, 3 replicate readings should be made at approximately 30- to 60-second intervals.  Blood pressure is recorded as the average of these three 
readings.  A single pulse measurement should be made simultaneously with at least one of the readings at each time point (Section 9.4.2. Vital Signs).
gh 12-lead ECGs (single) will be performed locally and will be locally (machine) read.
ih TB test(s) include PPD, QuantiFERON®-TB Gold, and T SPOT®.  See Exclusion Criterion [29] for details of TB testing.  In countries where the 
QuantiFERON-TB Gold test or T-SPOT is available, either test may be used instead of the PPD TB test.  The QuantiFERON-TB Gold test must be performed 
centrally; the T-SPOT must be performed locally.  Note:  Exception:  Patients with a history of active or latent TB who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was completed, have no clinical features of active TB, and have a screening chest 
x-ray with no evidence of active TB are not required to undergo the protocol-specific TB testing (i.e., PPD, QuantiFERON®-TB Gold, or T SPOT®) but must 
have a chest x-ray at screening (i.e.:  chest imaging performed within the past 6 months will not be accepted).
ji For those patients with a PPD placed at Visit 1, the PPD must be read 2 to 3 days (48 to 72 hours) post-Visit 1.  Purified protein derivative does not need to be 
read at the site, but must be read by a trained medical professional and results must be presented to the site at Visit 2.
kj A chest x-ray (posterior-anterior view) will be performed at screening unless chest imaging (excluding ultrasound) has been performed within the past 6 
months and the imaging and reports are available for review by the investigator.
lk Prior to randomization, there must be documentation of a patient having met at least 4 of 11 Revised Criteria for Classification of Systemic Lupus 
Erythematosus according to the 1997 Update of the 1982 ACR criteria for classification of SLE (Tan et al. 1982; Hochberg et al. 1997).  See Inclusion 
Criterion [3].
ml Suicidal ideation and behavior subscales excerpt; adapted for the assessment of 11 preferred ideation and behavior categories.  C-SSRS and Self-Harm 
Supplement Form should be completed after collection of unsolicited adverse events.
nmThe Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form.

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on Patient eligibility must be reviewed and confirmed by an eligibility review committee prior to randomization.  At Visit 2, patients will be randomized with 
stratification in IWRS, by total SLEDAI-2K score from Screening, corticosteroid dose at baseline, and region.  The Screening eGFR result must also be 
entered into IWRS for appropriate dose adjustment to occur if necessary.
po ePRO devices (daily patient diaries) should be dispensed to all patients at screening and will need to be collected from screen-failed patients.  Patients are 
encouraged to bring the ePRO device to every visit; however, if they do not bring the device, this will not be a protocol deviation.  For patients NOT entering 
the LTE, the patient diary will be returned at Visit 801 or the patient’s last visit.  For patients entering the LTE, the patient diary will be returned at Visit 16.
qp Worst Pain NRS, Worst Joint Pain NRS, Worst Fatigue NRS, Joint Stiffness Duration, Joint Stiffness Severity NRS, and PGI-S will be collected on an 
electronic patient diary daily (ePRO device) starting at Visit 1 (screening) through Visit 16 (or Visit 801 for those not entering the LTE Study JAIM) and 
should be completed prior to any clinical assessments on days when study visits occur.
rq SLE assessments must be completed by a physician and will be documented on an eCOA (electronic clinical outcome assessment) device.
sr Patient-reported questionnaires will be administered via an on-site eCOA device and should be administered prior to any clinical assessments.
ts For patients who are positive for HCV antibody, a follow-up test for HCV RNA will be performed automatically.  Patients who are positive for HCV antibody 
and negative for HCV RNA may be enrolled.
ut For patients who are positive for HBcAb, a follow-up test for HBV DNA will be performed automatically.  Patients who are positive for HBcAb and negative 
for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive, regardless of HBsAb status or level, must undergo HBV DNA testing per the
schedule of events (see Section 9.4.8 for details of HBV DNA monitoring).
vu For all women of child-bearing potential, a serum pregnancy test (central laboratory) will be performed at Visit 1.  Urine pregnancy tests (local laboratory) 
will be performed at Visit 2 prior to randomization and at all subsequent study visits.
wvFor female patients ≥50 and <55 years of age who have had a cessation of menses for at least 6 and less than 12 months, an FSH test will be performed to 
confirm non-child-bearing potential (FSH ≥40 mIU/mL).
xwClinical chemistry will include the following value calculated by the central laboratory from serum creatinine:  estimated glomerular filtration rate (eGFR; 
calculated using the Modification of Diet in Renal Disease [MDRD] isotope dilution mass spectrometry traceable method).
yx Fasting lipid profile. Patients should not eat or drink anything except water for 12 hours prior to sample collection.  If a patient attends these visits in a 
nonfasting state, the sample should still be collected.  This will not be considered a protocol violation.
zbb
Urine should be collected as a clean catch sample.
aaz
See Section 9.5 for details.
bbaa
Patients choosing not to provide consent for whole blood samples to be collected for pharmacogenetic research will still be eligible to participate in the 
study.

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4. 
Objectives and Endpoints
Table JAIA.2.
Objectives and Endpoints
Other Secondary (Non-Multiplicity Controlled)

To evaluate the effect of baricitinib 4-mg or 2-mg 
QD plus SoC compared to placebo plus SoC on 
SLE disease activity.

Change from baseline in total SLEDAI-2K scores 
over time through Week 52.

Change from baseline in PGA score over time 
through Week 52.

Proportion of patients achieving an SRI-4 response 
over time through Week 52.

Proportion of patients achieving an SRI-5, -6, -7, 
and -8 response over time through Week 52.

Proportion of patients achieving reduction of ≥4 
points from baseline in SLEDAI-2K score at Week 
52.

Proportion of patients with no new British Isles 
Lupus Assessment Group (BILAG) A or and no 
more than 1 new BILAG B disease activity score at 
Week 52.

Proportion of patients with no worsening (defined as 
an increase of ≥0.3 points [10 mm] from baseline) in 
the Physician’s Global Assessment of Disease 
Activity at Week 52.

Proportion of patients achieving a British Isles Lupus 
Assessment Group Based Composite Lupus 
Assessment (BICLA) response at Week 52, defined 
as: 
Reduction of all baseline BILAG A to B/C/D and 
baseline BILAG B to C/D, and no BILAG 
worsening in other organ systems, where 
worsening is defined as ≥1 new BILAG A or ≥2 
new BILAG B
No worsening from baseline in SLEDAI-2K, 
where worsening is defined as an increase from 
baseline of >0 points in SLEDAI-2K
No worsening from baseline in participants' lupus 
disease activity, where worsening is defined by an 
increase ≥0.30 points on a 3-point PGA visual 
analogue scale (VAS).
5.1.
Overall Design
Treatment Period
…
Investigational product will be taken daily for 52 weeks.  In some circumstances, due to COVID-
19 related logistical issues, Visit 16 may be completed outside of the protocol specified 

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timeframe, thus the treatment period may be extended.  Where allowed locally, additional IP 
(typically not to exceed 1 extra month’s supply) may be dispensed to prevent interruption of 
study drug.  Clinical assessments and laboratory samples, including additional PK sampling, will 
be obtained at scheduled visits according to the Schedule of Activities (Section 2).  Special 
timing considerations of administration of investigational product relative to PK sample 
collection at study visits are described in Section 9.5.
Follow-up Period: Patients who complete the treatment period of the study through Week 52 
(Visit 16) are eligible to participate in the long-term extension (LTE), Study I4V-MC-JAIM
(JAIM).  In some circumstances, due to COVID-19 related logistical issues, patients who were 
unable to complete Visit 16 in the protocol specified timeframe and had study drug temporarily 
interrupted, but otherwise completed the treatment period, may be eligible to participate in Study 
JAIM.  Patients who do not participate in the LTE, as well as those who discontinue JAIA study 
treatment early, will have a post-treatment follow-up visit (Visit 801) approximately 4 weeks 
after the last dose of investigational product.
6.1.
Inclusion Criteria
Patient Characteristics
[9]
Male or nonpregnant, nonbreastfeeding female patient
d. The following contraception methods are considered acceptable (the 
patient should choose 2, and 1 must be highly effective [defined as less 
than 1% failure rate per year when used consistently and correctly]):

Highly effective birth control methods:  

Combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:  oral, 
intravaginal, or transdermal

Progestogen- only containing hormonal contraception associated 
with inhibition of ovulation:  oral, injectableintravaginal, or 
implantabletransdermal

intrauterine device (IUD)/intrauterine hormone-releasing system 
(IUS)
…
…6.2. Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
Medical Conditions
…
[32]
Have received a JAK inhibitor or TYK-2 inhibitor.
6.4.
Screen Failures

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Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened one time.  The interval between initial screening failure and rescreening Visit 1 
should be at least 4 weeks.  When rescreening is performed the individual must sign a new ICF, 
repeat all screening procedures as described in the Schedule of Activities, and will be assigned a 
new identification number.
7.7.
Concomitant Therapy
Patients will maintain their usual medication regimen for SLE and for any other concomitant 
diseases throughout the study unless specifically excluded in the protocol (see Section 6.2, 
Exclusion Criteria).  Patients taking these medications should be on chronic stable doses at the 
time of randomization, as specified by the Inclusion Criteria (Section 6.1, Inclusion Criterion 
[8]).
…
Any changes to the patient’s medication must be discussed with the investigator.  Treatments for 
SLE or other concurrent illnesses may be reduced for safety reasons. Patients should be 
instructed to consult the investigator or other appropriate study personnel at the site before taking 
any new medications or supplements.
…
7.7.2. Prohibited Changes in Concomitant Therapy
Initiation of or increase in dose of an antimalarial or immunosuppressant is not permitted during 
the treatment period.  Patients requiring an initiation or increase above baseline dose of 
antimalarials or immunosuppressants, as defined in the SAP, during the treatment period will be 
discontinued from the study drug (see Section 8.1.12).
Patients requiring an increase above the baseline dose of corticosteroid for SLE during the 
treatment period, other than the permitted burst, as defined in the SAP, will be discontinued from 
study drug (see Section 8.1.12).
7.8.
Treatment after the End of the Study
7.8.1. Study Extensions
Patients who complete this study through Week 52 (Visit 16) may be eligible to participate in 
Study JAIM, if enrollment criteria for Study JAIM are met. In some circumstances, due to 
COVID-19 related logistical issues, patients who were unable to complete Visit 16 in the 
protocol specified timeframe and had study drug temporarily interrupted, but otherwise 
completed the treatment period, may be eligible to participate in Study JAIM.
9.1.
Efficacy Assessments
9.1.1. Primary Efficacy Assessment

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…
•
No new BILAG A orand no more than 1 new BILAG B disease activity scores (Section 
9.1.1.2); and
…
9.1.2.10.
British Isles Lupus Assessment Group Based Composite Lupus Assessment 
The BICLA is a composite index used to assess disease activity in SLE.  The BILAG component 
is used to capture clinically meaningful improvement in disease activity, while the BILAG, 
SLEDAI-2K, and Physician’s Global Assessment of Disease Activity components ensure that the 
improvement in overall disease is not accompanied by disease worsening in other organ systems.  
The BICLA response is defined as follows:

Reduction of all baseline BILAG A to B/C/D and baseline BILAG B to C/D, and no 
BILAG worsening in other organ systems, where worsening is defined as ≥1 new 
BILAG A or ≥2 new BILAG B

No worsening from baseline in SLEDAI-2K, where worsening is defined as an 
increase from baseline of >0 points in SLEDAI-2K

No worsening from baseline in participants' lupus disease activity, where worsening 
is defined by an increase ≥0.30 points on a 3-point PGA visual analogue scale (VAS)
9.4.10.1Venous Thromboembolic Event Assessment
If a patient develops clinical features of a DVT or PE, appropriate local laboratory tests and 
imaging should be performed, as necessary, for the diagnosis of the event.  For confirmed cases, 
additional laboratory testing is recommended as outlined in Appendix 5.  All suspected VTEs
events will be independently adjudicated by a blinded Clinical Event Committee.
10.1.
Sample Size Determination
…
An additional 10% (75 patients) may be enrolled due to COVID-19 related trial impacts.
Sample size and power estimates were obtained from nQuery® Advisor 7.0 using the χ2 test of 
equal proportions.
10.3.
Statistical Analyses
10.3.1. General Statistical Considerations
…
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.  Complete details of the planned analyses will be documented in the SAP.
For all analyses, Week 52 is considered to be equivalent to Visit 16, even if the timing of Visit 
16 was not within the protocol defined window.

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10.3.1.1Analysis Methods
…
Missing data for patients who have COVID-19-related issues (that are not related to an adverse 
event of COVID-19 infection) may be imputed using alternative method, based on consultation 
with regulatory bodies, as appropriate.  Specific imputation methodologies, for this subgroup of 
patients, will be detailed in the SAP prior to the primary endpoint database lock.
10.3.1.2Missing Data Imputation
…

Nonresponder imputation (NRI): For analysis of categorical efficacy and health 
outcomes variables such as SRI-4, missing data will be imputed using an NRI method.  
Patients who discontinue treatment early, increase use of corticosteroids above the 
baseline dose other than the permitted burst, as defined in the SAP, or have initiation of 
or an increase above baseline dose in immunosuppressant or antimalarial treatment, as 
defined in the SAP, any time after baseline will be defined as nonresponders.  In some 
circumstances, due to COVID-19 related logistical issues, patients may require reduction 
or discontinuation of concomitant medications such as antimalarials due to unavailability, 
or discontinuation of immunosuppressants due to local guidelines.  These patients may 
require initiation or increase in dose of other medications, such as steroids, to replace the 
discontinued medications.  These medications changes may not define patients as 
nonresponders.

Mixed-model repeated measure (MMRM):  For continuous variables, the primary analysis 
will be a MMRM analysis with a missing at random assumption for handling missing 
data.  This analysis takes into account both missingness of data and the correlation of the 
repeated measurements.  For patients who increase use of corticosteroids above the 
baseline dose other than the permitted burst, as defined in the SAP, or have initiation of 
or an increase above baseline dose in immunosuppressant or antimalarial treatment, as 
defined in the SAP, any time after baseline, any observed data after that visit will be 
excluded from the MMRM analysis.  Observed data after permanent discontinuation of 
investigational product will be analyzed as observed, with the exception of any data that 
occur after increase in use of corticosteroids above the baseline dose other than the 
permitted burst, or initiation of or an increase above baseline dose in immunosuppressant 
or antimalarial treatment.  In some circumstances, due to COVID-19 related logistical 
issues, patients may require reduction or discontinuation of concomitant medications 
such as antimalarials due to unavailability, or discontinuation of immunosuppressants due 
to local guidelines.  These patients may require initiation or increase in dose of other 
medications, such as steroids, to replace the discontinued medications.  For these specific 
COVID-19 cases, data will be treated as observed.

…

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Missing data for patients who have COVID-19-related issues (that are not related to an adverse 
event of COVID-19 infection) may be imputed using alternative methods, based on consultation 
with regulatory bodies, as appropriate.  Specific imputation methodologies, for this subgroup of 
patients, will be detailed in the SAP prior to the primary endpoint database lock.
10.3.3.1Primary Analyses
The primary efficacy measure is SRI-4 response (defined in Section 9.1.1).  A logistic regression 
model with Firth correction (as described in Section 10.3.1.1) will be used to test the treatment 
difference between baricitinib 4-mg and placebo in the proportion of patients achieving SRI-4 
response at Week 52.  Missing data will be imputed using the NRI method described in Section 
10.3.1.2.  Missing data for patients who have COVID-19-related issues (that are not related to an 
adverse event of COVID-19 infection) may be imputed using alternative method, based on 
consultation with regulatory bodies, as appropriate.  Specific imputation methodologies, for this 
subgroup of patients, will be detailed in the SAP prior to the primary endpoint database lock.
10.3.3.2 Major Secondary Analyses
…
Treatment comparisons in the proportion of patients achieving a binary response will be 
analyzed using logistic regression with Firth correction.  Treatment comparisons in the 
continuous measures will be analyzed using MMRM.  Treatment comparisons for time to first 
flare will be analyzed using a Cox proportional hazards model.  These methods are described in 
Section 10.3.1.1.  Missing data for the binary outcome measures will be imputed using the NRI 
method described in Section 10.3.1.2. Missing data for patients who have COVID-19-related 
issues (that are not related to an adverse event of COVID-19 infection) may be imputed using 
alternative method, based on consultation with regulatory bodies, as appropriate.  Specific 
imputation methodologies, for this subgroup of patients, will be detailed in the SAP prior to the 
primary endpoint database lock.
10.3.6. Interim Analyses
…
Access to the unblinded data will be limited to the DMC and statisticians providing the data.  
These statisticians will be independent from the study team.  The study team will not have access 
to the unblinded data.  Only the DMC is authorized to evaluate unblinded interim efficacy and 
safety analyses. The study sites will receive information about interim results ONLY if they need 
to know for the safety of their patients.  The DMC may request to review efficacy data to 
investigate the benefit/risk relationship in the context of safety observations for ongoing patients 
in the study. However, the study will not be stopped for positive efficacy results, and there is no
planned futility assessment. Hence, there will be no alpha adjustment for these interim analyses. 

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Adjustments to type I error will be made if an unplanned futility analysis for efficacy is 
performed.
In addition to the planned safety-related interim analyses, interim efficacy analyses may be 
conducted prior to completion of the study.  Using predefined thresholds, the trial may be 
stopped if the probability of the trial meeting its primary efficacy endpoint falls below an 
acceptable level.  The DMC charter will describe the precise decision guidelines governing the 
interim analyses.  The trial will not be stopped for positive efficacy; therefore, no alpha 
adjustment is needed.
In addition to the DMC members, a limited number of pre-identified individuals may gain access 
to the limited unblinded data, as specified in the unblinding plan, prior to the final database lock, 
in order to initiate the population PK/PD model development processes.  These analyses will not 
be considered interim analyses.  Information that may unblind the study during the analyses will 
not be reported to study sites or blinded study team until the study has been unblinded.

Leo Document ID = 80ea86ce-3caa-4cb9-ac5c-1c44d0819a7a
Approver: 
Approval Date & Time: 16-Apr-2020 21:28:45 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 20-Apr-2020 10:48:01 GMT
Signature meaning: Approved
PPD
PPD