A Randomized, Double-Blind, Placebo-Controlled, Parallel- Group, Phase 2 Study of Baricitinib in Patients With Systemic Lupus Erythematosus (SLE)
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Sponsor: Eli Lilly and Company

Protocol I4V-MC-JAHH 
A Randomized, Double-Blind, Placebo-Controlled, Parallel- Group, Phase 2 Study of Baricitinib 
in Patients with Systemic Lupus Erythematosus (SLE) 
NCT02708095 
Approval Date: 11-Dec-2015 

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Protocol I4V-MC-JAHH
A Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group, Phase 2 Study of Baricitinib in Patients with Systemic 
Lupus Erythematosus (SLE)
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)
Study I4V-MC-JAHH is a Phase 2, multicenter, randomized, double-blind, placebo-
controlled, parallel-group, outpatient, 24-week study designed to evaluate the efficacy and 
safety of baricitinib 4-mg and 2-mg in patients with SLE receiving standard therapy.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 11-Dec-2015 GMT

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Table of Contents
Section
Page
1.
Protocol Synopsis................................................................................................................9
2.
Introduction ......................................................................................................................12
2.1.
Background..................................................................................................................12
2.2.
Study Rationale............................................................................................................14
2.3.
Benefit/Risk Assessment..............................................................................................15
3.
Objectives and Endpoints..................................................................................................16
4.
Study Design.....................................................................................................................18
4.1.
Overview of Study Design ...........................................................................................18
4.2.
End of Trial Definition.................................................................................................19
4.3.
Scientific Rationale for Study Design...........................................................................19
4.4.
Justification for Dose ...................................................................................................21
5.
Study Population...............................................................................................................22
5.1.
Inclusion Criteria..........................................................................................................22
5.1.1.
Entry Criteria .......................................................................................................22
5.1.2.
Enrollment Criteria ..............................................................................................22
5.2.
Exclusion Criteria ........................................................................................................23
5.2.1.
Entry Criteria .......................................................................................................23
5.2.2.
Enrollment Criteria ..............................................................................................27
5.3.
Screen Failures.............................................................................................................30
5.4.
Lifestyle and/or Dietary Requirements .........................................................................30
6.
Treatment..........................................................................................................................31
6.1.
Treatments Administered .............................................................................................31
6.2.
Method of Treatment Assignment ................................................................................31
6.2.1.
Selection and Timing of Doses.............................................................................31
6.3.
Blinding .......................................................................................................................32
6.4.
Packaging and Labeling ...............................................................................................32
6.5.
Preparation/Handling/Storage.......................................................................................32
6.6.
Dose Modification........................................................................................................33
6.7.
Treatment Compliance .................................................................................................33
6.8.
Concomitant Therapy...................................................................................................33
6.9.
Treatment after Study Completion................................................................................34
6.9.1.
Continued Access.................................................................................................34
7.
Discontinuation Criteria ....................................................................................................35
7.1.
Discontinuation from Study Treatment.........................................................................35

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7.1.1.
Interruption of Investigational Product .................................................................35
7.1.2.
Permanent Discontinuation of Investigation Product ............................................36
7.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................37
7.1.4.
Patients Lost to Follow-Up...................................................................................38
8.
Study Assessments and Procedures ...................................................................................39
8.1.
Efficacy Assessments...................................................................................................39
8.1.1.
Primary Efficacy Assessment Scale......................................................................39
8.1.1.1.
SLEDAI-2K ...................................................................................................39
8.1.2.
Secondary Efficacy and Exploratory Assessments................................................39
8.1.2.1.
SLE Responder Index-4 (SRI-4).....................................................................39
8.1.2.2.
Physician’s Global Assessment of Disease Activity........................................39
8.1.2.3.
BILAG2004 ...................................................................................................40
8.1.2.4.
28 Tender Joint Count & 28 Swollen Joint Count ...........................................40
8.1.2.5.
Cutaneous Lupus Erythematosus Disease Area and 
Severity Index (CLASI)..................................................................................40
8.1.2.6.
SLEDAI Flare Index (SFI)..............................................................................40
8.1.2.7.
SLICC/ACR Damage Index............................................................................40
8.1.3.
Appropriateness of Assessments ..........................................................................41
8.2.
Adverse Events ............................................................................................................41
8.2.1.
Serious Adverse Events........................................................................................41
8.2.2.
Adverse Events and Laboratory Tests of Special Interest 
(AESIs)................................................................................................................42
8.2.2.1.
Suspected Unexpected Serious Adverse Reactions..........................................42
8.2.2.2.
Reasonably Anticipated Serious Adverse Events ............................................43
8.2.3.
Complaint Handling.............................................................................................43
8.3.
Treatment of Overdose.................................................................................................43
8.4.
Safety Assessments ......................................................................................................43
8.4.1.
Electrocardiograms ..............................................................................................43
8.4.2.
Vital Signs ...........................................................................................................43
8.4.3.
Laboratory Tests ..................................................................................................44
8.4.4.
Hepatitis B Virus (HBV) DNA Monitoring ..........................................................44
8.4.5.
Chest X-ray and Tuberculosis Testing..................................................................44
8.4.6.
Quick Inventory of Depressive Symptomatology Self-Rated–
16 (QIDS-SR16)....................................................................................................44
8.4.7.
Safety Monitoring ................................................................................................45
8.5.
Pharmacokinetics .........................................................................................................45
8.6.
Pharmacodynamics ......................................................................................................46
8.7.
Genetics .......................................................................................................................47
8.7.1.
Whole Blood Sample for Pharmacogenetic Research ...........................................47

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8.8.
Biomarkers...................................................................................................................47
8.9.
Health Outcomes..........................................................................................................48
8.9.1.
Patient’s Global Assessment of Disease Activity..................................................48
8.9.2.
Brief Pain Inventory (BPI)–Worst Pain Numeric Rating 
Scale (NRS) .........................................................................................................48
8.9.3.
Brief Pain Inventory (BPI)–Worst Joint Pain NRS ...............................................48
8.9.4.
Brief Fatigue Inventory (BFI)–Worst Fatigue NRS ..............................................48
8.9.5.
Short-Form 36-item Health Survey v2 (SF-36).....................................................49
9.
Statistical Considerations and Data Analysis.....................................................................50
9.1.
Determination of Sample Size ......................................................................................50
9.2.
General Statistical Considerations ................................................................................50
9.2.1.
General Considerations for Analyses....................................................................50
9.2.2.
Analysis Populations............................................................................................51
9.2.3.
Baseline Definition ..............................................................................................51
9.2.4.
Missing Data Imputation......................................................................................51
9.2.5.
Adjustment for Multiple Comparisons..................................................................52
9.2.6.
Adverse Events/Laboratory Results of Special Interest.........................................52
9.3.
Treatment Group Comparability...................................................................................52
9.3.1.
Patient Disposition...............................................................................................52
9.3.2.
Patient Characteristics..........................................................................................52
9.3.3.
Concomitant Therapy...........................................................................................52
9.3.4.
Treatment Compliance .........................................................................................52
9.4.
Primary and Secondary Analyses .................................................................................52
9.4.1.
Primary Analyses.................................................................................................52
9.4.2.
Secondary Analyses .............................................................................................53
9.4.3.
Exploratory Analyses...........................................................................................53
9.5.
Safety Analyses............................................................................................................54
9.5.1.
Adverse Events ....................................................................................................55
9.5.2.
Clinical Laboratory Tests .....................................................................................55
9.5.3.
Vital Signs, Physical Findings, and Other Safety Evaluation ................................56
9.6.
Pharmacokinetic/Pharmacodynamic Analyses..............................................................56
9.7.
Other Analyses.............................................................................................................56
9.7.1.
Health Outcomes..................................................................................................56
9.7.2.
Subgroup Analyses. .............................................................................................56
9.8.
Interim Analyses ..........................................................................................................57
10.
Study Governance Considerations.....................................................................................58
10.1. Regulatory and Ethical Considerations, Including the Informed 
Consent Process ...........................................................................................................58

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10.1.1.
Informed Consent.................................................................................................58
10.1.2.
Ethical Review.....................................................................................................58
10.1.3.
Regulatory Considerations ...................................................................................58
10.1.4.
Investigator Information.......................................................................................59
10.1.5.
Protocol Signatures ..............................................................................................59
10.1.6.
Final Report Signature .........................................................................................59
10.2. Data Quality Assurance................................................................................................59
10.2.1.
Data Capture System............................................................................................60
10.3. Study and Site Closure .................................................................................................60
10.3.1.
Discontinuation of Study Sites .............................................................................60
10.3.2.
Discontinuation of the Study................................................................................60
11.
References ........................................................................................................................61

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List of Tables
Table
Page
Table JAHH.1.
Objectives and Endpoints...............................................................................16
Table JAHH.2.
Treatment Regimens......................................................................................31
Table JAHH.3.
Criteria for Temporary Interruption of Investigational Product.......................35
Table JAHH.4.
Study JAHH Exploratory Analyses................................................................54

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List of Figures
Figure
Page
Figure JAHH.1. Illustration of study design for Clinical Protocol I4V-MC-JAHH...................19

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................65
Appendix 2.
Schedule of Activities....................................................................................70
Appendix 3.
Clinical Laboratory Tests...............................................................................76
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................79

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1. Protocol Synopsis
Title of Study:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study of Baricitinib in Patients with 
Systemic Lupus Erythematosus (SLE)
Rationale: 
Systemic lupus erythematosus (SLE) is a chronic, debilitating autoimmune disease that is characterized by the 
presence of autoreactive B cells and elevated levels of autoantibodies, which directly damage the body’s cells and 
tissues.  SLE can affect multiple organ systems simultaneously or sequentially, and follows an unpredictable clinical 
course where periods of relatively stable disease are followed by flares and/or periods of active disease that can 
ultimately lead to irreversible damage to tissues and organ systems. 
Baricitinib is an orally available, selective Janus kinase (JAK) inhibitor with excellent potency and selectivity for 
JAK1 and JAK2 and less potency for JAK3 or Tyrosine kinase 2 (TYK2; Fridman et al. 2010).  This activity profile 
suggests that baricitinib may inhibit cytokines implicated in SLE such as type I interferon (IFN; JAK1/TYK2), type 
II IFN-γ, interleukin (IL)-6 (JAK1/JAK2/TYK2), and IL-23 (JAK2/TYK2) as well as other cytokines that may have 
a role in SLE, including granulocyte-macrophage colony stimulating factor (JAK2/JAK2) and IL-12 (JAK2/TYK2).  
The potential impact of baricitinib on the IFN pathway is highly relevant to SLE, as clinical and preclinical studies 
have established that this pathway is involved in the pathogenesis of SLE.  
Clinical studies have established that baricitinib is effective in autoimmune/autoinflammatory diseases involving the 
joints, skin, and kidneys.  Baricitinib was effective at reducing swollen and tender joints in patients with rheumatoid 
arthritis (RA; I4V-MC-JADA [Phase 2] and I4V-MC-JADW and I4V-MC-JADX [Phase 3]), was effective at 
reducing disease severity in patients with moderate to severe plaque psoriasis (Menter et al. 2014), and was effective 
at reducing the urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease (Tuttle et al. 
2015).  The mechanism of action, combined with demonstration of clinical benefit in inflammatory diseases 
involving joints, skin and kidneys, provides the rationale for evaluating baricitinib in SLE.
Objectives/Endpoints:
Objectives
Endpoints
Primary
To evaluate the effect of baricitinib 4-mg daily (QD) or
2-mg QD compared to placebo on remission of SLE 
arthritis and/or rash in patients with SLE receiving 
concomitant standard therapy over 24 weeks.
Change in the proportion of patients who achieve 
remission of arthritis and/or rash as defined by the 
Systemic Lupus Erythematosus Disease Activity Index 
2000 (SLEDAI-2K) at Week 24 compared to baseline.
Secondary
To evaluate the effect of baricitinib 4-mg QD or 2-mg
QD compared to placebo on overall SLE disease 
activity in patients with SLE receiving concomitant 
standard therapy over 24 weeks.

Change in the proportion of patients achieving SLE 
Responder Index (SRI)-4 response at Week 24 
compared to baseline.  SRI-4 response is defined as: 
o
Reduction of ≥4 points from baseline in 
SLEDAI-2K score; 
o
No new British Isles Lupus Assessment Group 
(BILAG) A or no more than 1 new BILAG B 
disease activity scores; and
o
No worsening (defined as an increase of 
≥0.3 points [10 mm] from baseline) in the 
Physician’s Global Assessment of Disease 
Activity.

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Objectives
Endpoints

Change in the proportion of patients achieving a 
reduction of ≥4 points from baseline in SLEDAI-2K 
score at Week 24 compared to baseline.

Change in SLEDAI-2K total score at Week 24 
compared to baseline.
To evaluate the effect of baricitinib 4-mg QD or 2-mg
QD compared to placebo on the Patient’s Global 
Assessment of Disease Activity in patients with SLE 
receiving concomitant standard therapy over 24 weeks.

Change in Patient’s Global Assessment of Disease 
Activity at Week 24 compared to baseline.
To characterize the pharmacokinetics (PK) of 
baricitinib 4-mg QD or 2-mg QD in patients with SLE 
receiving concomitant standard therapy over 24 weeks.

Plasma baricitinib concentrations will be analyzed 
using a population PK (popPK) approach.
Summary of Study Design:  
Study I4V-MC-JAHH (JAHH) is a Phase 2 multicenter, randomized, double-blind, placebo-controlled, parallel-
group, outpatient, 24-week study evaluating the efficacy and safety of baricitinib 4-mg and 2-mg in patients with 
SLE receiving standard therapy.
Treatment Groups and Duration:  
Patients will be randomized at Week 0 to 1 of 3 treatment groups, baricitinib 4-mg daily, baricitinib 2-mg daily, or 
placebo.  The maximum total study duration will be up to 34 weeks over 3 periods (Screening Period:  up to 6 weeks 
prior to randomization; Double-Blinded Treatment Period:  24 weeks; Follow-up Period:  4 weeks after the last dose 
of investigational product).
Number of Patients: 
This study will include approximately 300 patients with SLE who will be randomized 1:1:1 to 1 of 2 dose groups of 
baricitinib or placebo (100 patients per treatment group).
Statistical Analysis:
Unless otherwise specified, the efficacy, health outcomes, and safety analyses will be conducted on the modified 
intent-to-treat (mITT) population.
Comparisons between baricitinib 4-mg or 2-mg and placebo will be performed for all analyses in the treatment 
period. Baseline will be defined as the last available value before the first dose of investigational product for both 
efficacy and safety analyses.
Treatment comparisons of categorical efficacy variables will be made using a logistic regression analysis with 
treatment, baseline disease activity (SLEDAI-2K <10 versus SLEDAI-2K ≥10), baseline anti double-stranded
deoxyribonucleic acid (anti-dsDNA) status (positive; negative), and region in the model.  The proportions and 95% 
confidence interval (CI) will be reported. Missing data will be imputed using the nonresponder imputation (NRI)
method. 

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Treatment comparisons of continuous efficacy and health outcome variables will be made using mixed-effects 
models for repeated measures (MMRM) model with treatment, baseline score, baseline disease activity (SLEDAI-
2K <10 versus SLEDAI-2K ≥10), baseline anti-dsDNA status (positive; negative), region, visit, and the interaction 
of treatment-by-visit as fixed factors.  An unstructured covariance matrix will be used to model the within-patient 
variance-covariance errors.  Type III sums of squares for the least squares (LS) means will be used for the statistical 
comparison; the 95% CI will also be reported.  Treatment group comparisons with placebo at Week 24 and other 
visits will be tested.
Fisher exact test will be used for all adverse events (AEs), baseline, discontinuation, and other categorical safety 
data. Continuous vital signs and laboratory values will be analyzed by an analysis of covariance (ANCOVA) with 
treatment and baseline values in the model.  Other continuous safety variables will be analyzed by t-tests, unless 
otherwise stated.

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2. Introduction
2.1.
Background
Systemic lupus erythematosus (SLE) is a chronic, debilitating autoimmune disease that is 
characterized by the presence of autoreactive B cells and elevated levels of autoantibodies, which 
directly damage the body’s cells and tissues.  SLE can affect multiple organ systems 
simultaneously or sequentially, and follows an unpredictable clinical course where periods of 
relatively stable disease are followed by flares and/or periods of active disease that can 
ultimately lead to irreversible damage to tissues and organ systems.
SLE is predominately a disease of women (~9:1, female to male), often beginning in adolescence 
or early adulthood.  It affects approximately 1 in 1000 people in the United States (US) and is 
more common in African-Americans, with as many as 1 in 330 African-American women 
afflicted with SLE (Lim et al. 2014; Somers et al. 2014).  Additionally, SLE appears to be more 
severe in African-Americans, Asian-Americans, and Latinos compared to Caucasians (Pons-
Estel et al. 2004).
Clinically, SLE presents with varying signs and symptoms, including arthralgia/arthritis, skin 
rash, alopecia, pleuritis, pericarditis, nephritis, vasculitis, stroke, seizure, thrombocytopenia, 
anemia, photosensitivity, and the presence of autoantibodies directed to nuclear antigens.  Skin 
and joint disease are the most frequent features at diagnosis.  Age, USA African race/ethnicity, 
Systemic Lupus Erythematosus Disease Activity Index 2000 (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 risk of death in 
patients with SLE compared to the general population (Yurkovich et al. 2014).  Thus, there 
remains substantial unmet medical need for individuals who suffer from SLE.
Standard of care for SLE includes corticosteroids, nonsteroidal anti-inflammatory drugs 
(NSAIDs), antimalarial agents, immunosuppressive agents, and cytotoxic agents; however, there 
are relatively few drugs approved for treatment of SLE.  For example, in the US, approved 
therapies for SLE include aspirin, antimalarials, corticosteroids, and belimumab.  In general, 
treatment regimens are similar around the world and are tailored to the severity of disease. 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 corticosteroid sparing agents to reduce chronic 
exposure to corticosteroids.

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The current standard of care (SoC) therapies have broad effects on immune and inflammatory 
pathways and have been associated with short-term and long-term morbidity.  For example, 
long-term use of corticosteroids is associated with cataracts, osteoporosis, avascular necrosis, 
increased infection, 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 mortality 
and morbidity, 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 interferon (IFN) signaling 
pathway.  Up-regulation of genes associated with the activation of type I IFN signaling, referred 
to as a type I IFN signature, is seen in approximately 70% of patients with SLE (Bauer et al.
2006; Higgs et al. 2011).  Not all autoimmune diseases are associated with a pronounced type I
IFN signature; for example, internal data have suggested that only approximately 15% of the 
patients with rheumatoid arthritis (RA) in a Phase 2 baricitinib trial (I4V-MC-JADA [JADA]) 
had a similar type I IFN signature.  However, 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) levels, decreased complement levels, and increased risk of 
severe flares (Bauer et al. 2009; Statistics-Development/Discovery, Eli Lilly and Company, 
2015).  Multiple studies have demonstrated that patients with SLE have a pronounced IFN 
signature.  This observation has been confirmed using microarray analyses from the tabalumab 
Phase 3 SLE studies in which approximately two-thirds of patients had an elevated IFN signature
(Chaussabel et al. 2008; Berthier et al. 2012; Lauwerys et al. 2013).  Additionally, monocytes 
from patients with SLE demonstrated an IFN-α2a imprint that included the upregulation of 
several signal transducer and activator of transcription (STAT) proteins (Smiljanovic et al.
2012).  These studies and others have provided a scientific rationale for targeting the type I IFN 
signature as a therapeutic option for SLE (Mathian et al. 2015).  Indeed, this signature is 
associated with a variety of chemokines that provide a basis for further lymphoid and myeloid 
cell infiltration into target organs (Gonzalez-Navajas et al. 2012).  While approaches targeting 
specific type I IFNs, primarily alpha, have not been successful, these approaches fail to target all 
type I IFNs, including beta, and the involvement of other cytokines including IL-6, type II IFN, 
and others that signal through the Janus kinase/JAK/STAT pathways (Kirou and Gkrouzman
2013).  Therefore, treatment of SLE with baricitinib or other JAK inhibitors is an area of intense 
interest.
Baricitinib (also previously known as LY3009104 and INCB028050) is a potent and selective 
small molecule inhibitor of JAK1 and JAK2 enzymes that is currently under development for the 

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treatment of inflammatory conditions such as RA, diabetic kidney disease, psoriasis, and atopic 
dermatitis.
Through 10 August 2015, approximately 4300 subjects have received baricitinib, including 
healthy subjects, and patients with RA, psoriasis, diabetic kidney disease, rare auto-inflammatory 
syndromes, with various degrees of renal impairment, and with hepatic dysfunction.  Baricitinib 
has been administered as single doses ranging from 1- to 40-mg and as repeat oral doses ranging 
from 2- to 20-mg to healthy subjects. Baricitinib has also been administered to patients with RA 
at doses up to 15-mg daily for 4 weeks, 10-mg daily for 24 weeks, 8-mg daily for 76 weeks, and 
lower doses up to 4-mg daily for up to approximately 5 years.  
2.2.
Study Rationale
Baricitinib is an orally available, selective JAK inhibitor with excellent potency and selectivity 
for JAK1 and JAK2 and less potency for JAK3 or Tyrosine kinase 2 (TYK2; Fridman et al. 
2010).  This activity profile suggests that baricitinib may inhibit cytokines implicated in SLE 
such as type I IFN (JAK1/TYK2), type II IFN-, IL-6 (JAK1/JAK2/TYK2), and IL-23 
(JAK2/TYK2) as well as other cytokines that may have a role in SLE, including granulocyte-
macrophage colony stimulating factor (JAK2/JAK2) and IL-12 (JAK2/TYK2).  The potential 
impact of baricitinib on the IFN pathway is highly relevant to SLE, as clinical and preclinical 
studies have established that this pathway is involved in the pathogenesis of SLE.  Evidence that 
baricitinib will down-modulate this signature has been seen at the messenger ribonucleic acid 
(mRNA) level through analysis of samples from patients treated with baricitinib in the psoriasis 
and RA programs and at the protein level in the diabetic nephropathy (DN) program.  Decreases 
in circulating levels of chemokines associated with this signature have been seen at the protein 
level in DN (Brosius et al. 2015; Tuttle et al. 2015) and in evaluating type I IFN transcripts in the 
small subset of RA patients that were characterized in a Phase 2 study as having an elevated type 
I IFN signature (Statistics-Development/Discovery, Eli Lilly and Company, 2015).  Studies 
performed by the Goldbach-Mansky group at the National Institutes of Health (NIH) in patients 
with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures 
(CANDLE) have shown that treatment with baricitinib resulted in decreased IFN signature, and 
this reduction in IFN signature was consistent with an improvement in clinical symptoms
(Montealegre et al. 2015).  There are current investigations underway to decrease the IFN 
signature through the use of a monoclonal antibody (anifrolumab) that targets the type I IFN 
receptor.  While targeting the IFN signature in this manner has shown to be effective in SLE 
(Furie et al. 2015), it may not be sufficient.  Data from the tabalumab Phase 3 SLE studies
demonstrated up-regulation of IL-6 related genes, IL-2 receptor, IL-12, and oncostatin M, all of 
which signal through the JAK/STAT pathways and would not be anticipated to be directly 
modulated by therapeutic strategies which only target the IFN pathway.  Therefore, baricitinib 
may prove to be an effective treatment as it targets multiple cytokines that have been linked to 
SLE whose expression is dependent on JAK signaling. 
Clinical studies have established that baricitinib is effective in treating autoimmune/
autoinflammatory diseases involving the joints, skin, and kidneys.  Baricitinib was effective at 
reducing swollen and tender joints in patients with RA (JADA [Phase 2], and I4V-MC-JADW 

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and I4V-MC-JADX [JADW and JADX, Phase 3]), was effective at reducing disease severity in 
patients with moderate to severe plaque psoriasis (Menter et al. 2014), and was effective at 
reducing urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease 
(Tuttle et al. 2015).  The mechanism of action, combined with demonstration of clinical benefit 
in inflammatory diseases involving joints, skin, and kidneys, provides a compelling rationale for 
evaluating baricitinib in SLE.
2.3.
Benefit/Risk Assessment
More information about the known and expected benefits, risks, serious adverse events (SAEs),
and reasonably anticipated adverse events (AEs) of baricitinib are to be found in the 
Investigator’s Brochure (IB).  

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3.
Objectives and Endpoints
Table JAHH.1 shows the objectives and endpoints of the study.
Table JAHH.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the effect of baricitinib 4-mg daily (QD) or
2-mg QD compared to placebo on remission of SLE 
arthritis and/or rash in patients with SLE receiving 
concomitant standard therapy over 24 weeks.
Change in the proportion of patients who achieve 
remission of arthritis and/or rash as defined by the 
SLEDAI-2K at Week 24 compared to baseline.
Secondary
To evaluate the effect of baricitinib 4-mg QD or 2-mg 
QD compared to placebo on overall SLE disease activity 
in patients with SLE receiving concomitant standard 
therapy over 24 weeks.

Change in the proportion of patients achieving SLE 
Responder Index 4 (SRI-4) response at Week 24 
compared to baseline.  SRI-4 response is defined as: 
o
Reduction of ≥4 points from baseline in 
SLEDAI-2K score; 
o
No new British Isles Lupus Assessment Group 
(BILAG) A or no more than 1 new BILAG B 
disease activity scores; and
o
No worsening (defined as an increase of 
≥0.3 points [10 mm] from baseline) in the 
Physician’s Global Assessment of Disease 
Activity.

Change in the proportion of patients achieving a 
reduction of ≥4 points from baseline in SLEDAI-2K 
score at Week 24 compared to baseline.

Change in SLEDAI-2K total score at Week 24 
compared to baseline.
To evaluate the effect of baricitinib 4-mg QD or 2-mg 
QD compared to placebo on the Patient’s Global 
Assessment of Disease Activity in patients with SLE 
receiving concomitant standard therapy over 24 weeks.

Change in the Patient’s Global Assessment of 
Disease Activity at Week 24 compared to baseline.
To characterize the pharmacokinetics (PK) of baricitinib 
4-mg QD or 2-mg QD in patients with SLE receiving 
concomitant standard therapy over 24 weeks.

Plasma baricitinib concentrations will be analyzed 
using a population PK (popPK) approach.
Exploratory
To evaluate the effect of baricitinib 4-mg QD or 2-mg 
QD compared to placebo on SLE arthritis and 
mucocutaneous disease activity in patients with SLE 
receiving concomitant standard therapy over 24 weeks.

Continuous and categorical endpoints based on joint 
counts

Continuous and categorical endpoints based on the 
Cutaneous Lupus Erythematosus Disease Area and 
Severity Index (CLASI).
To evaluate the effect of baricitinib 4-mg QD or 2-mg
QD compared to placebo on overall SLE disease activity 
in patients with SLE receiving concomitant standard 
therapy over 24 weeks.

Time to and proportion of patients experiencing first 
flare (any severity), first mild/moderate flare, and 
first severe flare defined by the SLEDAI Flare Index
(SFI).

Change in SLICC/ACR Damage index score at Week 
24 compared to baseline.

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Objectives
Endpoints
To evaluate the corticosteroid sparing effect of 
baricitinib 4-mg QD or 2-mg QD compared to placebo 
in patients with SLE receiving concomitant standard 
therapy over 24 weeks.

Change in proportion of patients receiving 
≥10 mg/day prednisone at baseline able to reduce 
prednisone (or equivalent) dose to ≤7.5-mg for 
12 consecutive weeks between Week 12 and 
Week 24.
To evaluate the effect of baricitinib 4-mg QD or 2-mg
QD compared to placebo on serologic markers of SLE in 
patients with SLE receiving concomitant standard 
therapy over 24 weeks.

The difference in reduction of IFN signature between 
treatment groups at Week 12 and Week 24 compared 
to baseline.

In patients with elevated anti-dsDNA at baseline, 
change in anti-dsDNA level at Week 12 and Week 
24 compared to baseline.

In patients with low C3 and C4 at baseline, change in 
C3 and C4 levels at Week 12 and Week 24 compared 
to baseline.
To evaluate the effect of baricitinib 4-mg QD or 2-mg
QD compared to placebo on patient-reported outcomes 
(PROs) in patients with SLE receiving concomitant 
standard therapy over 24 weeks.

Change in worst pain item from the Brief Pain
Inventory (BPI) at Week 12 and 24 compared to 
baseline

Change in worst joint pain item from the BPI at 
Week 12 and 24 compared to baseline

Change in worst fatigue item from the Brief Fatigue 
Inventory (BFI) at Week 12 and 24 compared to 
baseline

Change 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 12 and 24 compared to baseline.
To explore dose/exposure response relationships with 
key efficacy (such as SLEDAI-2K) and safety (such as 
hematologic parameters) endpoints of interest.

The relationship between baricitinib PK and key 
efficacy and safety endpoints will be characterized 
using popPK/pharmacodynamics (popPK/PD)
modeling.

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4.
Study Design
4.1.
Overview of Study Design
Study I4V-MC-JAHH (JAHH) is a Phase 2, multicenter, randomized, double-blind, placebo-
controlled, parallel-group, outpatient, 24-week study evaluating the efficacy and safety of 
baricitinib 4-mg and 2-mg in patients with SLE receiving standard therapy.
Approximately 300 patients will be randomized 1:1:1 to receive baricitinib 4-mg daily, 
baricitinib 2-mg daily, or placebo (100 patients per treatment group).  Patients will be stratified at 
randomization according to disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), anti-dsDNA 
status (positive; negative), and region (defined in the statistical analysis plan [SAP]).
The study consists of 3 periods:

Screening Period:  Patients meeting entry criteria begin the 3- to 42-day screening 
period by signing the informed consent form (ICF).  Patients will be screened for study 
enrollment eligibility at Visit 1, and eligible patients will be randomized at Visit 2
(Week 0).

Double-Blinded Treatment Period:  Randomized patients begin the 24-week double-
blind, placebo-controlled treatment period at Visit 2 (Week 0) and administer 
investigational product daily through Visit 9 (Week 24).
All patients will continue on stable background standard therapy consisting of 
corticosteroids, NSAIDs (for which the NSAID use is intended for treatment of signs and 
symptoms of SLE), a single antimalarial (such as hydroxychloroquine or chloroquine), 
and/or a single immunosuppressant (such as methotrexate [MTX], azathioprine, or 
mycophenolate).  NSAID, antimalarial, and immunosuppressant doses should remain 
stable throughout the Double-Blinded Treatment Period.  Decreases in corticosteroid 
dose, as well as subsequent increases to less than or equal to the baseline dose will be 
permitted between Week 0 and Week 16.  No changes in corticosteroid dose (increases or 
decreases) will be permitted between Week 16 and Week 24.  Further details regarding 
concomitant therapy are in Section 6.8.
Initiation or increase in dose of NSAIDs (for which the NSAID use is intended for 
treatment of signs and symptoms of SLE), corticosteroids (above the baseline dose 
through Week 16, or any increase after Week 16), antimalarials, and/or 
immunosuppressants is not permitted after randomization. After randomization, patients 
requiring the abovementioned initiation or increase in dose of SLE SoC medications, as 
well as those meeting discontinuation criteria, will be discontinued from investigational 
product and complete the study procedures for an early termination visit (ETV).

Follow-Up Period: Patients who complete the study through Visit 9 (Week 24), as well 
as those who discontinue 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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Figure JAHH.1 illustrates the study design.  The 3 dosing regimens are described in Section 6.1.  
As this is a double-blind study, the blinding procedure described in Section 6.3 will be followed.
Abbreviations:  n = number of patient per treatment group; QD = daily; V = visit; W = week.
a
For those patients with a purified protein derivative (PPD) placed at Visit 1, Visit 1a must occur 48 to 72 hours 
post-Visit 1 for PPD to be read.  
b
All patients should return for a post-treatment follow-up visit (V801) 4 weeks after the last dose of 
investigational product.
Figure JAHH.1.
Illustration of study design for Clinical Protocol I4V-MC-JAHH.
4.2.
End of Trial Definition
End of the trial is the date of the last visit, last scheduled procedure shown in the Schedule of 
Activities (Appendix 2), or date of discontinued participation for the last patient.
4.3.
Scientific Rationale for Study Design
The scientific rationale for the primary endpoint of this study is based on analyses from 2 large 
tabalumab SLE Phase 3 trials with a similar patient population involving over 2200 patients 
(Isenberg et al. 2015; Merrill et al. 2015).  The primary endpoint in these trials was SRI-5.  The 
goal of these analyses was to characterize the clinical symptoms most responsible for achieving 
responder status with SRI-5, and then use this information to design a more efficient trial with 
clinically relevant endpoints.
To achieve SRI-5, one needs improvement in SLEDAI, with no worsening in BILAG or 
Physician’s Global Assessment of Disease Activity.  In the Phase 3 trials, BILAG and 
Physician’s Global Assessment of Disease Activity contributed minimal information to SRI-5, as 
fewer than 1% of patients achieved a ≥5-point reduction in SLEDAI score, but failed the 
endpoint due to worsening of BILAG or Physician’s Global Assessment of Disease Activity.  
These data provided the rationale to focus on SLEDAI as the primary driver of clinical response.

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The SLEDAI is a weighted disease activity index that measures presence or absence of disease in 
9 organ systems.  Disease activity in the mucocutaneous, musculoskeletal, or immunologic organ 
systems was present in over 70% of patients at baseline, with over 98% of patients having 
mucocutaneous and/or musculoskeletal disease at baseline.  In contrast, in the other 6 organ 
systems these diseases were present in ≤15% of patients.  These data provided the rationale to 
focus on mucocutaneous and musculoskeletal disease as the primary driver of clinical response.
The 9 SLEDAI organ systems are composed of specific disease symptoms.  The musculoskeletal 
organ system consists of arthritis and myositis.  Arthritis was the most prevalent symptom at 
baseline (>80% of patients) while myositis was rare (~1% of patients).  The mucocutaneous 
organ system includes rash, alopecia, and mucosal ulcer.  Rash was the most common symptom 
in this organ system (~70% of patients), followed by alopecia (~55%) and mucosal ulcer 
(~30%).  These data, in consultation with SLE experts, provided the rationale to focus on 
remission of arthritis and rash as the primary endpoint in the clinical trial.
This study is designed to allow for an efficient evaluation of efficacy using clinically relevant 
endpoints, while still allowing examination of the full range of SLE disease signs and symptoms.  
SLEDAI, BILAG, and CLASI assessments will be completed at most visits, enabling the 
evaluation of the entire spectrum of SLE disease activity in this trial, although the primary 
endpoint is focused on arthritis and rash.  
The observation that baricitinib was effective at reducing albuminuria in patients with diabetic 
kidney disease is also relevant to the design of the trial (Tuttle et al. 2015).  As in most SLE 
trials, patients with severe, active glomerulonephritis are excluded.  However, there is interest in 
collecting preliminary data on a subset of patients to determine if baricitinib has a positive 
impact on the symptoms of lupus nephritis.  Thus, patients with a history of nephritis and current 
stable renal disease are encouraged to enroll.  
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 are allowed to receive concomitant SoC, including corticosteroids, 
NSAIDs, antimalarials, and/or immunosuppressants.  
In order to minimize the confounding effects of concomitant medications, no increases above 
baseline are allowed for corticosteroids, immunosuppressants, NSAIDs, or antimalarials during 
the trial.  This strict control over corticosteroids and immunosuppressants is supported by data 
from the Phase 3 SLE trials discussed above, where less than 20% of patients in any group 
required an increase in prednisone over the first 24 weeks, and fewer than 10% required an
increase in prednisone in the first 8 weeks.
Patients with intolerable or exacerbating disease requiring initiation or increase in doses of 
corticosteroids, NSAIDs, antimalarials, or immunosuppressants will be discontinued from study 
treatment and will be treated as nonresponders for the efficacy analyses.  

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4.4.
Justification for Dose 
The baricitinib doses of 4-mg and 2-mg administered orally once daily were selected for SLE 
based on RA studies (JADA [Phase 2] and JADW and JADX [Phase 3]) and a psoriasis study 
(I4V-MC-JADP, Phase 2) described in the IB.
In these studies, doses of 4-mg and 2-mg daily were generally well tolerated based on the AE
profile and infrequent discontinuations of baricitinib dosing.  The anticipated on-target, dose-
limiting toxicity is a small decline in hemoglobin and hematocrit values resulting from the 
finding that erythropoietin signals via the JAK2/STAT5 signal transduction pathway 
(Klingmüller et al. 1997; Vera et al. 2008).  This decline in hemoglobin and hematocrit has been 
seen to occur in higher-dose groups (8-mg daily) upon initiation of treatment and then stabilize.
Baricitinib 4-mg and 2-mg daily doses have shown efficacy in RA with an acceptable safety 
profile.  There was no additional efficacy associated with an 8-mg dose in the Phase 2 RA study;
thus, only 4-mg and 2-mg have been studied in the RA Phase 3 program.  The 4-mg daily dose 
has demonstrated an earlier onset and a more consistent efficacy than 2-mg daily in RA studies. 
In psoriasis, 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.  
However, 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.  The 2-mg dose did show 
numeric improvements in efficacy compared with placebo.  
The only patient factor thus far that has been identified to have a clinically relevant effect on the 
PK of baricitinib in completed RA, psoriasis, and DN studies is overall renal function.  Although 
it is currently not clear whether different disease conditions (such SLE versus RA) might result 
in different PK, aside from varying renal function associated with the disease states, the 
difference, if any, is not expected to be substantial.  It is therefore assumed that exposure at 2-mg 
and 4-mg in patients with SLE will be similar to that in RA, psoriasis, and DN patients studied, 
after accounting for renal function.  Thus, the highest baricitinib dose to be tested in SLE will be 
4-mg, which would be anticipated to show efficacy together with an acceptable safety profile, 
and also provide the opportunity to cross-reference to the large safety database from the RA 
Phase 3 program.  The lower dose of 2-mg also has the opportunity to show efficacy in SLE.  

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5.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
Patients are entered into the study once they have signed the ICF.  Patients may be assessed for 
study entry on the basis of readily available information (that is, information that does not 
require informed consent from the patient).
5.1.
Inclusion Criteria
5.1.1. Entry Criteria
Patients are eligible for entry into the study (eligible to sign the ICF) only if they are anticipated 
to meet all of the following entry criteria at screening (Visit 1):
Type of Patient and Disease Characteristics
[1]
Are at least 18 years of age. 
[2]
Have received a clinical diagnosis of SLE at least 24 weeks prior to screening, meeting 
at least 4 of the 11 Revised Criteria for Classification of Systemic Lupus 
Erythematosus according to the 1997 Update of the 1982 ACR (Tan et al. 1982; 
Hochberg et al. 1997) OR meeting at least 4 of the 2012 SLICC classification criteria
(Petri et al. 2012), including at least 1 clinical criterion and 1 immunologic criterion. 
[3]
Have history of a positive antinuclear antibody (ANA) or a positive anti-dsDNA (if 
available). 
[4]
Have active arthritis and/or rash due to SLE.
Informed Consent
[5]
Are able to read, understand, and give written informed consent.
5.1.2. Enrollment Criteria
Entered patients are eligible for enrollment into the study (eligible for randomization) only if 
they continue to meet all of the entry criteria above, and meet all of the following enrollment 
criteria at the time of randomization (Visit 2):
Type of Patient and Disease Characteristics
[6]
Have a positive ANA (HEp-2 ANA titer ≥1:80) and/or a positive anti-dsDNA 
(≥30 IU) as assessed by a central laboratory at screening.
Note:  The ANA and/or anti-dsDNA measurement may be repeated once 
within approximately 2 weeks of the initial value, and the value resulting from 
repeat testing may be accepted for enrollment eligibility if it meets the 
eligibility criterion.

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[7]
Have a SLEDAI-2K score ≥4 based on clinical symptoms (not including lab values) at 
randomization.
[8]
Have active arthritis and/or active rash as defined by the SLEDAI-2K at 
randomization.
5.2.
Exclusion Criteria
5.2.1. Entry Criteria
Patients are ineligible for entry into the study (ineligible to sign the ICF) if they are anticipated to 
meet any of the following entry exclusion criteria at screening (Visit 1):
Medical Conditions
[9]
Have active severe lupus nephritis as defined in exclusion criterion [50].
[10]
Have active severe central nervous system (CNS) lupus as defined in exclusion 
criterion [51].
[11]
Have experienced a clinically significant thrombotic event within 24 weeks of 
screening or are on anticoagulants and in the opinion of the investigator are not well 
controlled.
[12]
Have active fibromyalgia that, in the investigator’s opinion, would make it difficult to 
appropriately assess SLE activity for the purposes of this study.
[13]
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 in the 
12 weeks prior to screening.
a.
Patients with secondary Sjogren’s syndrome are not excluded.
[14]
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.
[15]
Have experienced any of the following within 12 weeks of screening:  myocardial 
infarction (MI), unstable ischemic heart disease, stroke, or New York Heart 
Association Stage IV heart failure.
[16]
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.
[17]
Are largely or wholly incapacitated permitting little or no self-care, such as being 
bedridden or confined to wheelchair.
[18]
Have an estimated glomerular filtration rate (eGFR) based on the most recent available 
serum creatinine of <50 mL/min/1.73 m2 (if available).

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[19]
Have a history of chronic liver disease with the most recent available aspartate 
aminotransferase (AST) or alanine aminotransferase (ALT) >2 times the upper limit of 
normal (>2 x ULN) or the most recent available total bilirubin 1.5 x ULN (if 
available).
[20]
Have a history of lymphoproliferative disease; or have signs or symptoms suggestive 
of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly 
(other than primarily due to SLE); or have active primary or recurrent malignant 
disease; or have been in remission from clinically significant malignancy for <5 years.
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 screening) clinically serious viral, 
bacterial, fungal, or parasitic infection.
Note: For example, a recent viral upper respiratory tract infection or uncomplicated 
urinary tract infection should not be considered clinically serious.
[22]
Have had symptomatic herpes zoster infection within 12 weeks prior to screening.
[23]
Have a history of disseminated/complicated herpes zoster (for example, 
multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic 
neuralgia).
[24]
In the opinion of the investigator, are at an unacceptable risk for participating in the 
study.
[25]
Have active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus 
(HCV), or human immunodeficiency virus (HIV).
[26]
Have had household contact with a person with active tuberculosis (TB) and did not 
receive appropriate and documented prophylaxis for TB.
[27]
Have evidence of active TB or have previously had evidence of active TB and did not 
receive appropriate and documented treatment.
Prior/Concomitant Therapy
[28]
Are currently receiving oral corticosteroids at doses >20-mg per day of prednisone (or 
equivalent) or have adjusted the dose of corticosteroids within 2 weeks of planned 
randomization.
[29]
Have received topical corticosteroids, other than stable doses of class 6 (mild, such as 
desonide) or class 7 (least potent, such as hydrocortisone), within 2 weeks of screening 
or within 4 weeks of planned randomization.  

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[30]
Have received oral or parenteral [intravenous (IV) or intramuscular (IM)]
corticosteroids at doses >40-mg per day of prednisone (or equivalent) within 6 weeks 
of screening or within 8 weeks of planned randomization, or are anticipated to require 
parenteral injection of corticosteroids during the study.
[31]
Have had a joint injected with intra-articular corticosteroids or hyaluronic acid within 
2 weeks of screening or within 4 weeks of planned randomization.
[32]
Have started treatment with or adjusted the dose of NSAIDs (for which the NSAID 
use is intended for treatment of signs and symptoms of SLE) within 2 weeks of 
screening or within 4 weeks of planned randomization.
[33]
Have started treatment with or adjusted the dose of an antimalarial (such as
hydroxychloroquine, chloroquine, quinacrine) within 10 weeks of screening or within 
12 weeks of planned randomization.
[34]
Have started treatment with or adjusted the dose of an immunosuppressant (such as
MTX, azathioprine, mycophenolate) within 10 weeks of screening or within 12 weeks 
of planned randomization.
[35]
Have received cyclophosphamide (or any other cytotoxic agent) within 12 weeks prior 
to screening.
[36]
Have received etanercept, infliximab, certolizumab, adalimumab, golimumab, or 
anakinra within 12 weeks of screening; tocilizumab, abatacept, ustekinumab, 
rituximab, belimumab, or any other B cell targeted therapies (approved or 
investigational) within 24 weeks of screening; or any other biologic therapy within 
4 weeks or 5 half-lives of screening, whichever is longer.
[37]
Have received intravenous immunoglobulin (IVIg) within 24 weeks of screening.
[38]
Have received plasmapheresis within 12 weeks of screening.
[39]
Have been exposed to a live vaccine within 12 weeks prior to planned randomization 
or are expected to need/receive a live vaccine during the course of the study (with the 
exception of herpes zoster vaccination).
a.
All patients who have not received the herpes zoster vaccine at screening will be 
encouraged (per local guidelines) to do so prior to randomization; vaccination 
must occur >4 weeks prior to randomization and start of investigational product.  
Patients will be excluded if they were exposed to herpes zoster vaccination within 
4 weeks of planned randomization.
b. Investigators should review the vaccination status of their patients and follow the 
local guidelines for vaccination of those ≥18 years of age with nonlive vaccines 
intended to prevent infectious disease prior to entering patients into the study.
Other Exclusions
[40]
Are pregnant or nursing at the time of screening.

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[41]
Are females of childbearing potential who do not agree to use 2 forms of highly 
effective birth control when engaging in sexual intercourse with a male partner while 
enrolled in the study and for at least 4 weeks following the last dose of investigational 
product.
a.
Females of nonchildbearing potential are defined as women 60 years of age, 
women 40 and <60 years of age who have had a cessation of menses for at least 
12 months, or women who are congenitally or surgically sterile (that is, have had 
a hysterectomy or bilateral oophorectomy or tubal ligation).
b. The following birth control methods are considered highly effective (the patient 
should choose 2 to be used with their male partner):
o oral, injectable, or implanted hormonal contraceptives
o condom with a spermicidal foam, gel, film, cream, or suppository
o occlusive cap (diaphragm or cervical/vault caps) with a spermicidal foam, gel, 
film, cream, or suppository
o intrauterine device
o intrauterine system (for example, progestin-releasing coil)
o vasectomized male (with appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate)
Note:  When local guidelines concerning highly effective methods of 
birth control differ from the above, the local guidelines must be 
followed. 
[42]
Are males who do not agree to use 2 forms of highly effective birth control (see 
above) while engaging in sexual intercourse with female partners of childbearing 
potential while enrolled in the study and for at least 4 weeks following the last dose of 
investigational product.
[43]
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.
[44]
Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug abuse 
within the 2 years prior to screening.
[45]
Have previously been randomized in this study or any other study investigating 
baricitinib.
[46]
Are unable or unwilling to make themselves available for the duration of the study 
and/or are unwilling to follow study restrictions/procedures.
[47]
Are currently enrolled in, or discontinued within 4 weeks prior to screening from any 
other clinical trial involving an investigational product or nonapproved use of a drug 
or device or concurrently enrolled in any other type of medical research judged not to 
be scientifically or medically compatible with this study.

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[48]
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.
[49]
Are Lilly or Incyte employees or either’s designee.
5.2.2. Enrollment Criteria
Entered patients are ineligible for enrollment into the study (ineligible for randomization) and 
should be discontinued from the study if they meet any of the entry exclusion criteria above, or 
meet any of the following enrollment exclusion criteria at the time of randomization (Visit 2):
Medical Conditions
[50]
Have severe active lupus nephritis, including urine protein/creatinine ratio 
>300 mg/mmol (as an estimate of approximate proteinuria >3g/day) or active urinary 
sediment with red blood cell cast(s), or histological evidence (if available) of diffuse
proliferative glomerulonephritis within the 12 weeks prior to screening.  
Note:  The lab measurements related to lupus nephritis may be repeated once within 
approximately 2 weeks of the initial values, and the values resulting from repeat 
testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
[51]
Have active severe CNS lupus including aseptic meningitis, cerebral vasculitis, 
demyelinating syndrome, myelopathy, acute confusional state, psychosis, acute 
inflammatory demyelinating polyradiculoneuropathy, mononeuropathy 
(single/multiplex), cranial neuropathy, plexopathy, status epilepticus, or cerebellar 
ataxia.
[52]
Have symptomatic herpes simplex at the time of randomization.
[53]
Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the 
investigator or the sponsor, are clinically significant and indicate an unacceptable risk 
for the patient’s participation in the study.
[54]
Have evidence of active TB as documented by a positive purified protein derivative 
(PPD) test (≥5-mm induration between approximately 2 and 3 days after application, 
regardless of vaccination history), medical history, clinical symptoms, and abnormal 
chest x-ray at screening.

The 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.
[55]
Have evidence of latent TB (as documented by a positive PPD test, no clinical 
symptoms consistent with active TB, and a normal chest x-ray at screening, or as 
outlined below) unless patient 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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
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) and will be excluded.

The 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 and will 
be excluded.  If the test is not negative, the test may be repeated once within 
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) and will 
be excluded.

Exceptions include patients with a history of active or latent TB who have 
documented evidence of appropriate treatment and with no history of re-exposure 
since their treatment was completed. (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 would still require a baseline chest x-ray.)  
[56]
Have a positive test for HBV defined as:
a.
positive for hepatitis B surface antigen (HBsAg), or
b. positive for anti-hepatitis B core antibody (HBcAb) but negative for hepatitis B 
surface antibody (HBsAb), or
c.
positive for HBcAb and positive for hepatitis B virus deoxyribonucleic acid 
(HBV DNA)
d. Patients in Japan (or elsewhere if required), are excluded if they are positive for 
HBsAg; or, are positive for HBcAb and/or HBsAb and positive for HBV DNA.
If any of the HB tests have an indeterminate result, confirmatory testing will be 
performed by an alternate method.
[57]
Have HCV (positive for anti-hepatitis C antibody with confirmed presence of HCV).
[58]
Have evidence of HIV infection and/or positive HIV antibodies.
Diagnostics Assessments
[59]
Have screening laboratory test values, including thyroid-stimulating hormone (TSH), 
outside the reference range for the population or investigative site that, in the opinion 
of the investigator, pose an unacceptable risk for the patient’s participation in the 
study.

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
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 are receiving stable 
thyroxine replacement therapy who have TSH marginally outside the laboratory’s 
normal reference range may participate if the treating physician has documented 
that the thyroxine replacement therapy is adequate for the patient.
Laboratory tests may be repeated once within approximately 2 weeks of the initial 
value, and the value resulting from repeat testing may be accepted for enrollment 
eligibility if it meets the eligibility criterion.
[60]
Have any of the following specific abnormalities on screening laboratory tests:
a.
ALT or AST >2 x ULN
b. total bilirubin ≥1.5 x ULN
c.
hemoglobin <9 g/dL (90.0 g/L)
d. total white blood cell (WBC) count <2500 cells/µL (<2.50x103/µL or <2.50 GI/L)
e.
neutropenia (absolute neutrophil count [ANC] <1200 cells/µL) (<1.20x103/µL or
<1.20 GI/L)
f.
lymphopenia (lymphocyte count <750 cells/µL) (<0.75x103/µL or <0.75 GI/L)
Note:  Patients may be enrolled with a lymphocyte count <750 cells/µL but 
≥500 cells/µL (<0.50x103/µL or <0.50 GI/L) if the low lymphocyte count is 
considered by the investigator to be a result of the underlying SLE disease or 
concomitant medications.
g. thrombocytopenia (platelets <50,000 cells/µL) (<50x103/µL or <50 GI/L)
h. eGFR (Modification of Diet in Renal Disease [MDRD]) <50 mL/min/1.73 m2.
In the case of any of the aforementioned laboratory abnormalities, the tests may be 
repeated once within approximately 2 weeks of the initial values, and values resulting 
from repeat testing may be accepted for enrollment eligibility if they meet the 
eligibility criterion.
Other Exclusions
[61]
Are women ≥40 and <60 years of age who have had a cessation of menses for at least 
1 year, have a follicle-stimulating hormone (FSH) value <40 mIU/mL, and do not 
agree to use 2 forms of highly effective methods of birth control when engaging in 
sexual intercourse with a male partner while enrolled in the study and for at least 
4 weeks following the last dose of investigational product, unless they are congenitally 
or surgically sterile (that is, have had a hysterectomy, bilateral oophorectomy, or tubal 
ligation).

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5.3.
Screen Failures
Patients who are entered into the study but do not meet the enrollment criteria for participation in 
this study (screen failure) may be re-screened once. The interval between screen failure and re-
screenings should be at least 4 weeks.  At the time of re-screening, the individual must sign a 
new ICF, repeat all necessary screening procedures, and will be assigned a new identification 
number.
5.4.
Lifestyle and/or Dietary Requirements
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.

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6.
Treatment
6.1.
Treatments Administered
This study involves a comparison of baricitinib 4-mg and baricitinib 2-mg administered orally 
once daily with placebo.  Table JAHH.2 shows the treatment regimens.
Table JAHH.2.
Treatment Regimens
Regimen
Dose
Week 0 through Week 24
Baricitinib 4-mg QD
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
2 placebo tablets: 1 matching baricitinib 4-mg and 1 matching baricitinib 2-mg
Abbreviations:  QD = daily.
The investigator or his/her designee is responsible for the following:

explaining the correct use of the investigational product to the patient or legal 
representative 

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.
6.2.
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 (Week 0).  Randomization 
will be stratified by disease activity (SLEDAI-2K <10; SLEDAI-2K ≥10), anti-dsDNA status 
(positive; negative), 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 2 bottles (Bottle A and Bottle B), each containing 
36 double-blind investigational product tablets to each patient, starting at Visit 2 (Week 0), and
at each visit through Visit 8 (Week 20).  Site personnel will confirm that they have located the 
correct bottles by entering a confirmation number found on the bottles into the IWRS.  Patients 
will be instructed to take 1 tablet from Bottle A and 1 tablet from Bottle B each day.  
6.2.1. Selection and Timing of Doses
The investigational product (1 tablet from Bottle A and 1 tablet from Bottle B) should be taken
without regard to food and, if possible, at approximately the same time every day to aid patient 
compliance.  Refer to Section 8.5, Pharmacokinetics, for specific instructions on dose timing at 
certain visits where a PK sample is drawn.

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6.3.
Blinding
This is a double-blind study.  All study assessments will be done by study personnel who are 
blinded to the patient’s treatment group.  Except in clinical circumstances where unblinding is 
required, the patients, investigators, Lilly study team, and any personnel interacting directly with 
patients or investigative sites will remain blinded to baricitinib and placebo assignment until 
after completion of the Double-Blinded Treatment Period.  It is expected that the need for 
unblinding a patient’s treatment prior to completion of the Double-Blinded Treatment Period will 
be extremely rare.  Every effort should be made to preserve the blind unless there is a compelling 
reason that knowledge of the specific treatment would alter the medical care of the patient.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s acute well-being requires knowledge of the patient’s treatment 
assignment.  All unblinding events are recorded and reported by the IWRS.
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 Lilly clinical research 
physician (CRP) or designee 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.
If an investigator, site personnel performing assessments, or patient is unblinded, patient 
discontinuation should be considered after discussion with the sponsor.  In cases where there are 
ethical reasons to have the patient remain in the study, the investigator must obtain specific 
approval from the Lilly CRP for the patient to continue in the study.
6.4.
Packaging and Labeling
The sponsor (or its designee) will provide the following investigational products:

tablets containing 4-mg of baricitinib (Bottle A)

tablets containing 2-mg of baricitinib (Bottle B)

placebo tablets to match baricitinib 4-mg tablets (Bottle A)

placebo tablets to match baricitinib 2-mg tablets (Bottle B).
Baricitinib 4-mg and 2-mg tablets and packaging will be identical in appearance to the respective
placebo tablets in order to maintain the blind.
Investigational product tablets will be provided in bottles containing 36 tablets.
Clinical trial materials will be labeled according to the country’s regulatory requirements.  
6.5.
Preparation/Handling/Storage
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, 

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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.
Follow storage and handling instructions on the investigational product packaging.
6.6.
Dose Modification
Not applicable.
6.7.
Treatment Compliance
Patient compliance with investigational product will be assessed at each visit during the 
treatment period (Visit 3 through Visit 9) by counting returned tablets.  Deviations from the 
prescribed dosage regimen should be recorded in the electronic case report form (eCRF).
A patient will be considered significantly noncompliant if he or she misses more than 20% of the 
prescribed doses of investigational product (full doses) during the study, unless the patient’s 
investigational product is withheld by the investigator for safety reasons.  Similarly, a patient 
will be considered significantly noncompliant if he or she is judged by the investigator to have 
intentionally or repeatedly taken 20% more than the prescribed amount of medication.
Patients will be counseled by study staff on the importance of taking the investigational product 
as prescribed, as appropriate.
Patients’ compliance will be further defined in the SAP.
6.8.
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 5.2,
Exclusion Criteria). Patients taking these medications should be on chronic stable doses at the 
time of randomization, as specified by the Entry Criteria (Section 5.2.1).
Concomitant SoC for SLE in this study can include corticosteroids, NSAIDs, a single 
antimalarial (such as chloroquine or hydroxychloroquine), and/or a single immunosuppressant 
(such as azathioprine, MTX, or mycophenolate).
Corticosteroid dose must be ≤20-mg per day of prednisone (or equivalent) and stable for 2 weeks
prior to randomization.  Increases in corticosteroid dose are not permitted after randomization.  
Decreases in corticosteroid dose will be permitted between Week 0 and Week 16.  If 
corticosteroid dose is decreased during this time period, subsequent increases, only to less than 
or equal to the baseline dose, will be permitted until Week 16.  No changes in corticosteroids 
(increases or decreases) will be permitted between Week 16 and Week 24.  Patients who require 
initiation or increase in dose of corticosteroids after randomization should be discontinued from 
investigational product, have an ETV, and proceed to the Follow-Up Period of the study.
Doses of NSAIDs (for which the NSAID use is intended for treatment of signs and symptoms of 
SLE), antimalarials, and immunosuppressants should not be adjusted during the Double-Blinded 
Treatment Period.  Patients who require initiation or increase in dose of NSAIDs (for which the 

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NSAID use is intended for treatment of signs and symptoms of SLE), antimalarials, or 
immunosuppressants after randomization should be discontinued from investigational product, 
have an ETV, and proceed to the Follow-Up Period of the study.
Any changes to the patient’s medication must be discussed with the investigator. 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.  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.
6.9.
Treatment after Study Completion
6.9.1. Continued Access
Baricitinib will not be made available after conclusion of the study.  Patients will be referred to 
their local treatment centers for continued therapy as clinically indicated.

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7.
Discontinuation Criteria
7.1.
Discontinuation from Study Treatment
7.1.1. 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.  
Except in cases of emergency, it is recommended that the investigator consult with Lilly (or its 
designee) before temporarily interrupting therapy for reasons other than those defined in 
Table JAHH.3 below. Retest timing and frequency is at the investigator’s discretion.
The investigator must obtain approval from Lilly (or its designee) before restarting 
investigational product that was temporarily discontinued because of an AE or abnormal 
laboratory value.  Investigational product must be held in the following situations and may be 
resumed as noted in Table JAHH.3.
Table JAHH.3.
Criteria for Temporary Interruption of Investigational Product
Hold investigational product if the following 
laboratory test results occur:
Investigational product may be resumed after 
approval from Lilly (or its designee) when:
WBC count <2000 cells/µL
(<2.00x103/µL or <2.00 GI/L)
WBC count 2500 cells/µL
(≥2.50x103/µL or ≥2.50 GI/L)
ANC <1000 cells/L
(<1.00x103/µL or <1.00 GI/L)
ANC ≥1200 cells/µL
(≥1.20x103/µL or ≥1.20 GI/L)
Lymphocyte count <500 cells/µL
(<0.50x103/µL or <0.50 GI/L)
Note:  IP can be continued with a lymphocyte count 
<500 cells/µL but ≥300 cells/µL (<0.30x103/µL or 
<0.30 GI/L) if the low lymphocyte count is 
considered by the investigator to be a result of the 
underlying SLE disease or concomitant medications.  
IP must be held for lymphocyte count <300 cells/µL, 
regardless of cause.
Lymphocyte count 750 cells/µL
(≥0.75x103/µL or ≥0.75 GI/L)
Note:  If IP is held for lymphocyte count 
<300 cells/µL, it may be resumed after approval from 
Lilly (or its designee) when the lymphocyte count is 
≥500 cells/µL if the low lymphocyte count is 
considered by the investigator to be a result of the 
underlying SLE disease or concomitant medications.
Platelet count <25,000/µL
(<25x103/µL or <25 GI/L)
Platelet count 50,000/µL
(≥50x103/µL or ≥50 GI/L)
eGFR <40 mL/min/1.73 m2 (from serum creatinine) 
eGFR 50 mL/min/1.73 m2 
ALT or AST >5 x 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
Severe infection that, in the opinion of the investigator, 
merits the IP being discontinued
Resolution of infection
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.

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7.1.2. Permanent Discontinuation of Investigation Product
Any patient who is permanently discontinued from investigational product for an AE or 
abnormal laboratory result should have the reason for investigational product discontinuation 
reported as the AE or abnormal laboratory value.  
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 
INR >1.5 x ULN

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 upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%).
Patients should be discontinued from the investigational product in the following circumstances:

WBC count <1000 cells/µL (1.00x103/µL or 1.00 GI/L)

ANC <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).
For lab values that meet permanent discontinuation thresholds, investigational product should be 
discontinued unless, in the opinion of the investigator, the lab abnormality is due to intercurrent 
illness or another identified factor. After consultation with the Lilly-designated medical monitor, 
the patient may be able to continue receiving investigational product.  Lab tests may be repeated 
within 1 week to confirm whether discontinuation criteria have been met. Furthermore, if 
investigational product is not discontinued due to intercurrent illness, the investigator must 
confirm the lab value no longer meets discontinuation thresholds following the resolution of the 
intercurrent illness or other identified factor.
In addition, patients will be discontinued from investigational product in the following 
circumstances:

Pregnancy

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
Malignancy (except for successfully treated basal cell or squamous epithelial skin 
cancers)

HBV DNA above the lower limit of quantification (LLOQ)
Note:  If the HBV DNA result is “target detected” (above the LLOQ), then the 
patient should be referred to a hepatology specialist immediately. 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 evaluation of individual patient risks and benefits.  Refer to 
Section 8.4.4 for additional instruction on HBV DNA monitoring.
Some possible reasons that may lead to permanent discontinuation include:

Enrollment in any other clinical trial 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)

Investigator Decision
o
the investigator decides that the patient should be discontinued from the study
o
if the patient, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication
(including initiation or increase in dose of NSAIDs [for which the NSAID use is 
intended for treatment of signs and symptoms of SLE], corticosteroids [above the 
baseline dose], antimalarials, and/or immunosuppressants) discontinuation from 
the investigational product occurs prior to introduction of the new agent

Patient Decision
o
the patient requests to be withdrawn from the study.
Patients who discontinue the investigational product early will have ETV procedures performed 
as shown in the Schedule of Activities (Appendix 2) and proceed to the Follow-Up Period of the 
study.
7.1.3. Discontinuation of Inadvertently Enrolled Patients
If the sponsor or investigator identify a patient who did not meet enrollment criteria and was 
inadvertently enrolled, a discussion must occur between the sponsor CRP and the investigator to 
determine if the patient may continue in the study.  If both agree it is medically appropriate to 
continue, the investigator must obtain documented approval from the sponsor CRP to allow the 
inadvertently enrolled patient to continue in the study with or without treatment with 
investigational product.

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7.1.4. Patients Lost to Follow-Up
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.  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.  

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8.
Study Assessments and Procedures
Appendix 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 3 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.
8.1.
Efficacy Assessments
8.1.1. Primary Efficacy Assessment Scale
8.1.1.1.
SLEDAI-2K
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, CVA; 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.  The primary endpoint in this study will 
assess remission of arthritis and/or rash as defined by the SLEDAI-2K.
8.1.2. Secondary Efficacy and Exploratory Assessments
8.1.2.1.
SLE Responder Index-4 (SRI-4)
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.  
SRI-4 response is defined as: 

Reduction of ≥4 points from baseline in SLEDAI-2K score; 

No new BILAG A or no more than 1 new BILAG B disease activity scores; and 

No worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in 
Physician’s Global Assessment of Disease Activity.
8.1.2.2.
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 

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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.
8.1.2.3.
BILAG2004
The BILAG2004 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 IV corticosteroids, 
immunomodulators, or high-dose anticoagulation along with high-dose corticosteroids or 
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.
8.1.2.4.
28 Tender Joint Count & 28 Swollen Joint Count
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.
8.1.2.5.
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
The 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.
8.1.2.6.
SLEDAI Flare Index (SFI)
The SFI uses the SLEDAI-2K 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 scores, new or worsening symptoms, 
and increases in medication use or hospitalization due to the disease activity.
8.1.2.7.
SLICC/ACR 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.

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8.1.3. Appropriateness of Assessments
All assessments made in this study are standard, widely used, and generally recognized as 
reliable, accurate, and relevant.
8.2.
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, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  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 via eCRF any change in the condition(s) and any 
new conditions as AEs. Investigators should record their assessment of the potential relatedness 
of each AE to protocol procedure, studied disease state, and/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.
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. 
8.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

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
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

considered significant by the investigator for any other reason:  important medical 
events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious, based upon appropriate medical judgment
Although all AEs after signing the ICF are recorded in the eCRF, SAE reporting 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, it needs to be reported 
ONLY 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 sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.
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 summary eCRF 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/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
8.2.2. Adverse Events and Laboratory Tests of Special Interest 
(AESIs)
Adverse events of special interest (AESIs) or laboratory results of special interest will include
severe or opportunistic infections; myelosuppressive events of anemia, leukopenia, neutropenia, 
lymphopenia, and   thrombocytopenia; thrombocytosis; and elevations in ALT or AST (>3 x
ULN) and total bilirubin (>2 x ULN).
8.2.2.1.
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 guidances or national regulatory requirements in participating countries 
require the reporting of SUSARs.  Lilly has procedures that will be followed for the recording 

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and expedited reporting of SUSARs that are consistent with global regulations and the associated 
detailed guidances.
8.2.2.2.
Reasonably Anticipated Serious Adverse Events
In the SLE population, the occurrence of renal failure/nephropathy, major cerebrocardiovascular 
events (including cardiovascular—death, MI, hospitalization for unstable angina, hospitalization 
for heart failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock due to MI, 
coronary revascularization procedure; neurologic—stroke; and peripheral vascular events), 
skeletal-related events (including osteoporosis), SLE flares, and serious infections are reasonably 
anticipated due to the disease state, comorbid conditions, and use of concomitant medications.  
The serious instances of these reasonably anticipated AEs will be reviewed in aggregate on a 
regular periodic basis to evaluate any numerical imbalances between treatment groups in SAEs 
for reporting to the Food and Drug Administration in the US.
8.2.3. 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.
8.3.
Treatment of Overdose
Refer to the IB.
8.4.
Safety Assessments
8.4.1. Electrocardiograms
For each patient, 12-lead standard ECGs should be collected locally according to the Schedule of 
Activities (Appendix 2).  Electrocardiograms may be obtained at additional times, when deemed 
clinically necessary.
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
patient receives the first dose of the investigational treatment should be reported to Lilly or its 
designee as an AE via eCRF.
8.4.2. Vital Signs
For each patient, vital signs measurements should be conducted according to the Schedule of 
Activities (Appendix 2).  
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of investigation product should be reported to 
Lilly or its designee as an AE via eCRF.

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8.4.3. Laboratory Tests
For each patient, laboratory tests detailed in (Appendix 3) should be conducted according to the 
Schedule of Activities (Appendix 2). 
Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of investigational product should be reported to Lilly or its 
designee as an AE via eCRF.
8.4.4. Hepatitis B Virus (HBV) DNA Monitoring
HBV 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 HBsAb status. 
If the HBV DNA result is above the LLOQ, then the patient should be referred to a hepatology 
specialist immediately.  In selected cases, investigators may temporarily continue investigation 
product in accordance with current immunomodulator management in the setting of HBV DNA 
positivity.  This option may be considered in consultation with the sponsor (or its designee) and 
evaluation of individual patient risks and benefits.
If a single result of “target detected” is obtained (a result above the LLOQ), the test should be 
repeated within approximately 2 weeks.  If the repeat test result is “target not detected,” 
monitoring may resume according to the Schedule of Activities.
For study sites in Japan (or elsewhere if required), if a patient is HBcAb positive and/or HBsAb 
positive and negative for HBV DNA at Visit 1, HBV DNA needs to be checked at least monthly 
and at the patient’s last visit.
8.4.5. Chest X-ray and Tuberculosis Testing 
A posterior-anterior view chest x-ray will be obtained locally, unless results from a chest x-ray 
obtained within 6 months prior to the study are available.  The chest x-ray will be reviewed by 
the investigator or his/her designee to exclude patients with active TB infection.  In addition, 
patients will be tested at screening and entry for evidence of active or latent TB as described in 
the Exclusion Criteria (Section 5.2).
8.4.6. Quick Inventory of Depressive Symptomatology Self-Rated–16
(QIDS-SR16)
The QIDS-SR16 is a 16-item, self-report 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, 4th Edition (APA 1994). Patients are 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:  sad mood, concentration, 

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self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance (initial, middle, and 
late insomnia or hypersomnia), decrease/increase in appetite/weight, and psychomotor 
agitation/retardation.  Additional information and the QIDS-SR16 questions may be found on the 
University of Pittsburgh Epidemiology Data Center web site (Inventory of Depressive 
Symptomatology/Quick Inventory of Depressive Symptomatology [WWW]) (Rush et al. 2003; 
Trivedi et al. 2004).
8.4.7. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
The Lilly CRP will monitor safety data throughout the course of the study.  Lilly will review 
SAEs within time frames mandated by company procedures.  The Lilly CRP 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, only 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.
If a study patient experiences elevated ALT ≥3 x ULN, ALP ≥2 x ULN, or elevated TBL ≥2 x
ULN, clinical and laboratory monitoring should be initiated by the investigator.  Details for 
hepatic monitoring depend upon the severity and persistence of observed laboratory test 
abnormalities.  To ensure patient safety and comply with regulatory guidance, the investigator is 
to consult with the Lilly CRP regarding collection of specific recommended clinical information 
and follow-up laboratory tests (see Appendix 4).
8.5.
Pharmacokinetics
Blood samples for PK analyses will be collected from all randomized patients in accordance with 
the Schedule of Activities (Appendix 2).  Plasma samples will be assayed for baricitinib using a 
validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method at a laboratory 
approved by Lilly or its designee.
On the day of Visit 2, after completion of baseline assessments (including baseline laboratory 
tests as outlined in the Schedule of Activities) and administration of investigational product, a 
single PK sample will be collected 15 to 30 minutes postdose.  It is important that apart from this 
single PK sample, all other baseline laboratory samples are taken PREdose.

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On the day of Visit 4 and Visit 7, a single predose PK sample will be collected for each visit.  
Patients will be advised not to take their investigational product prior to visiting the clinic. To 
reduce the number of blood draws, the predose PK sample may be drawn at the same time as 
other routine labs required at that visit. Patients can subsequently take their investigational 
product at any time during their visit to the clinic. The patient should be instructed to take a dose 
of investigational product from the new packages assigned at that visit. If a patient arrives at the 
clinic on the day of Visit 4 or Visit 7 after having taken the dose, the PK sample should be drawn 
with other routine labs randomly at any time postdose; the inability to collect predose samples 
will not be considered a protocol violation.
On the day of Visit 5, one PK sample will be taken between 1 and 3 hours postdose.  The visit 
should be scheduled to accommodate this sampling.  Patients will be advised to record the exact 
time when the dose was taken at home and report it to the site personnel.  Alternatively, patients 
may take their investigational product upon arrival to the clinic for their visit. To reduce the 
number of blood draws, the postdose PK sample may be drawn at the same time as other routine 
labs required at that visit.  The inability to collect postdose samples at the specified time will not 
be considered a protocol violation.
A single PK sample also is to be collected, if possible, from patients who discontinue the study
early. 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 any PK samples taken, the actual date and time of PK sample collection and the date and
time of last 2 doses prior to the PK sample should be recorded.  PK samples will be kept in 
storage at a laboratory facility designated by Lilly or its designee.  Only samples from active 
doses will be assayed (PK samples from patients on placebo will not be assayed).  PK samples 
may also be assayed for additional exploratory analyses.  Bioanalytical samples collected to 
measure investigational product concentration will be retained for a maximum of 1 year 
following the last patient visit for the study.  
8.6.
Pharmacodynamics
Plasma, serum, and urine samples will be collected for evaluation of pharmacodynamic (PD) 
markers, including, but not limited to anti-dsDNA, complement, anti-Sm, anti-RNP, anti-
SSA/Ro, and anti-SSB/La.
The markers will not include any markers of the patient’s genetic makeup.  Samples will be 
collected at the times noted in the Schedule of Activities.
Bioanalytical samples collected to measure PD markers will be identified by the patient number 
(coded) and retained for a maximum of 1 year following last patient visit for the study at a 
facility selected by Lilly or its designee. 

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8.7.
Genetics
8.7.1. Whole Blood Sample for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis as specified in the 
Schedule of Activities (Appendix 2) where local regulations allow.  
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 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)/investigational 
review boards (IRBs) impose shorter time limits, at a facility selected by Lilly or its designee.  
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.
8.8.
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 ribonucleic acid (RNA), 
proteins, lipids, and other cellular elements.
Serum, plasma, urine, and whole blood RNA samples for non-pharmacogenetic biomarker 
research will be collected at the times specified in the Schedule of Activities (Appendix 2) where 
local regulations allow.
Samples will be used for research on the drug target, disease process, variable response to 
baricitinib, pathways associated with SLE, IFN signature, 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 for a maximum 15 years after the last patient visit for the study, or for a 
shorter period if local regulations and ERBs impose shorter time limits, at a facility selected by 

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Lilly or its designee.  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 becomes commercially available.
8.9.
Health Outcomes 
The self-reported questionnaires will be administered prior to any clinical assessments according 
to the Schedule of Activities (Appendix 2) in countries where the questionnaires have been 
translated into the native language of the region and linguistically validated.  These instruments 
will be captured at the site via an electronic patient-reported outcomes (ePRO) device.
8.9.1. Patient’s Global Assessment of Disease Activity
The Patient’s Global Assessment of Disease Activity is a single-item, patient reported scale 
developed for the assessment of the patient’s overall rating of their disease activity due to SLE.  
The scale measures disease activity through a 5 point Likert scale ranging from 0 (“No disease 
activity”) to 4 (“Severe disease activity”) at its worst over the past 7 days (Felson et al. 1993; van 
Tuyl and Boers 2012).
8.9.2. Brief Pain Inventory (BPI)–Worst Pain Numeric Rating Scale
(NRS)
The BPI-sf modified is a 5-item, self-administered questionnaire developed for the rapid 
assessment of pain, and provides information on the intensity of pain (the sensory dimension) as 
well as the degree to which pain interferes with function (the reactive dimension). The BPI-sf 
modified also asks questions about pain relief, pain quality, and the patient’s perception of the 
cause of pain.  The worst pain item of the BPI-sf modified is a 1-item, self-administered question 
developed for the rapid assessment of pain intensity.  The worst pain item uses an 11-point scale 
from 0 (“No pain”) to 10 (“Pain as bad as you can imagine”) NRS. Since pain can be quite 
variable over a day, the worst pain item asks patients to rate their pain at its worst over the past 
7 days (Cleeland 1991; Cleeland and Ryan 1994).
8.9.3. Brief Pain Inventory (BPI)–Worst Joint Pain NRS
The worst joint pain item is adapted from the worst pain item of the BPI-sf modified.  It is a 
single-item, self-administered question developed for the rapid assessment of pain intensity of 
the joints.  The worst joint pain item uses an 11-point scale from 0 (“No joint pain”) to 10 (“Joint 
pain as bad as you can imagine”) NRS.  Since pain can be quite variable over a day, the worst 
joint pain item asks patients to rate their joint pain at its worst over the past 7 days 
(Cleeland1991; Cleeland and Ryan 1994).
8.9.4. Brief Fatigue Inventory (BFI)–Worst Fatigue NRS
The BFI is a brief patient-reported questionnaire for the rapid assessment of fatigue severity and 
the impact of fatigue on daily functioning.  The BFI contains 10 items; however, the first item is 
not included in the overall scoring of the scale as it asks about usual fatigue over the past week 
with the respondent answering “yes” or “no.” The remaining 9 items assess fatigue severity 

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(3 items) and impact of fatigue on daily functioning (6 items).  The worst fatigue item of the BFI 
is a brief patient-reported question for the rapid assessment of worst fatigue severity.  The item 
features an 11-point numeric scale (0 [“No fatigue”] to 10 [“Fatigue as bad as you can 
imagine”]) and asks patients to rate their fatigue at its worst over the past 7 days.  The BFI is 
implemented without a user manual.  The instructions for the completion are embedded within 
the questionnaire, and patients will read the instructions before responding to the corresponding 
item (Mendoza et al. 1999; Wolfe 2004).
8.9.5. Short-Form 36-item Health Survey v2 (SF-36)
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).

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9.
Statistical Considerations and Data Analysis
9.1.
Determination of Sample Size
Approximately 300 patients will be randomized in a 1:1:1 ratio to the baricitinib 4-mg, 2-mg, 
and placebo treatment groups.  With 100 patients per treatment group, this study will have 
approximately 81% power to detect a difference between baricitinib 4-mg or 2-mg and placebo 
of ≥20% in remission rates of rash and/or arthritis at Week 24.  The sample size was determined 
based on the chi-square test with 2-sided type I error of 5% and 40% remission rate of rash 
and/or arthritis in placebo treatment group.  The sample size calculation was performed using  
nQuery® Advisor 7.0 software.
9.2.
General Statistical Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company.
Efficacy analyses will be conducted on the modified intent-to-treat (mITT) population.  This set 
includes all data from all randomized patients receiving at least 1 dose of the investigational 
product according to the treatment the patients were assigned.
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated.
Any change to the planned 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 (CSR).  Additional exploratory analyses of the data will be 
conducted as deemed appropriate.
The SAP will provide analysis details.
9.2.1. General Considerations for Analyses 
In general, continuous data will be summarized in terms of the mean, standard deviation, 
minimum, maximum, median, and number of observations.  Categorical data will be summarized 
as frequency counts and percentages.
Comparisons between the baricitinib 4-mg or baricitinib 2-mg and placebo groups will be 
performed for all analyses for the Double-Blinded Treatment Period.  No adjustment for 
multiplicity will be done for these comparisons.
Treatment comparisons of categorical efficacy variables will be made using a logistic regression 
analysis with treatment, baseline disease activity (SLEDAI-2K <10 versus SLEDAI-2K ≥10), 
baseline anti-dsDNA status (positive; negative), and region in the model.  The proportions and 
95% confidence interval (CI) will be reported.  Missing data will be imputed using the NRI 
method. 
Treatment comparisons of continuous efficacy and health outcome variables will be made using 
mixed-effects models for repeated measures (MMRM) model with treatment, baseline score, 

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baseline disease activity (SLEDAI-2K <10 versus SLEDAI-2K ≥10), baseline anti-dsDNA status 
(positive; negative), region, visit, and the interaction of treatment-by-visit as fixed factors.  An 
unstructured covariance matrix will be used to model the within-patient variance-covariance 
errors.  Type III sums of squares for the least squares (LS) means will be used for the statistical 
comparison; the 95% CI will also be reported.  Treatment group comparisons with placebo at 
Week 24 and other visits will be tested.
Fisher exact test will be used for all AE, baseline, discontinuation, and other categorical safety 
data.  Continuous vital signs and laboratory values will be analyzed by an analysis of covariance 
(ANCOVA) with treatment and baseline values in the model.  Other continuous safety variables
will be analyzed based on t-tests, or as otherwise stated.
9.2.2. Analysis Populations
Unless otherwise specified, the efficacy, health outcomes, and safety analyses will be conducted 
on the mITT population, defined as all randomized patients who received at least one dose of 
investigational product, even if the patient does not receive the correct treatment, or otherwise 
does not follow the protocol.  Patients will be analyzed according to the treatment to which they 
were assigned.  Significant protocol violations will be described in the SAP.
Safety analyses for the post-treatment Follow-up Period will be conducted on the follow-up
population, defined as all randomized patients who received at least 1 dose of investigational 
product and have entered the post-treatment Follow-Up Period.  Patients will be analyzed 
according to the dosing regimen to which they were assigned in the Treatment Period.
9.2.3. Baseline Definition
Baseline will be defined as the last available value before the first dose of investigational product
for both efficacy and safety analyses.  In most cases, this will be the measure recorded at Week 0 
(Visit 2).  Change from baseline will be calculated as the visit value of interest minus the 
baseline value.  For the post-treatment Follow-up Period, the baseline is defined as the last 
nonmissing assessment on or prior to entering the post-treatment Follow-up Period, that is, on or 
prior to the Week 24 visit (Visit 9), or the end of treatment visit (including ETV).
9.2.4. Missing Data Imputation
The patients will be considered nonresponders for the NRI analysis if they do not meet the 
clinical response criteria (for example, remission of rash/arthritis, SRI-4) at Week 24.  All 
nonresponders at Week 24 as well as all patients who discontinue study treatment at any time 
prior to Week 24, for any reason, will be defined as nonresponders for the NRI analysis for all 
categorical analyses at Week 24.  Patients who require initiation or increase in dose of NSAIDs, 
corticosteroids, antimalarials, or immunosuppressants after randomization (as outlined in 
Section 6.8, Concomitant Therapy) will be analyzed as nonresponders from the day of initiation 
or increase in medication.  Randomized patients without at least 1 postbaseline observation will 
also be defined as nonresponders for the NRI analysis. MMRM is the primary analysis method 
for analyzing the continuous efficacy endpoints.  In this method no imputation is needed.  
However, a sensitivity analysis, the placebo multiple imputation (pMI) method will be used for 

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the selected analyses of the continuous endpoints at Visit 9 (Week 24). The pMI assumes that 
the statistical behavior of drug- and placebo-treated patients after discontinuing investigational 
product becomes that of placebo-treated patients.
9.2.5. Adjustment for Multiple Comparisons
No adjustment for multiple comparisons will be done.
9.2.6. Adverse Events/Laboratory Results of Special Interest
Adverse events or laboratory results of special interest include severe or opportunistic infections, 
myelosuppressive events of anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, 
thrombocytosis; and elevations in ALT/AST (≥3 x ULN) and total bilirubin (≥2 x ULN).  The 
number of AESIs as well as the percentage of patients who experienced at least 1 AESI will be 
summarized by treatment group.
9.3.
Treatment Group Comparability
9.3.1. Patient Disposition
A detailed description of patient disposition by treatment will be summarized with reasons for 
discontinuation.
9.3.2. Patient Characteristics
Summary tables by treatment group will be generated for demographics and patient 
characteristics at baseline (Visit 2), for historic diagnoses, and for preexisting conditions.
9.3.3. Concomitant Therapy
Concomitant therapy will be summarized and reported for the Double-Blinded Treatment Period.  
A listing of patients using excluded medications during the period will be provided.
9.3.4. Treatment Compliance
Compliance to therapy will be reported for the Double-Blinded Treatment Period as described in 
Section 6.7.
9.4.
Primary and Secondary Analyses
9.4.1. Primary Analyses
The primary endpoint is the proportion of patients who achieve remission of arthritis and/or rash 
as defined by the SLEDAI-2K at Week 24. Either arthritis or rash (as defined by the SLEDAI-
2K) are required to be present at baseline.  If only arthritis is present at baseline, then arthritis has 
to be absent at Week 24 to meet the primary endpoint.  If only rash is present at baseline, then 
rash has to be absent at Week 24 to meet the primary endpoint.  If both arthritis and rash are 
present at baseline, then the primary endpoint is met if either arthritis, or rash, or both arthritis 
and rash are absent at Week 24.

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Treatment comparison between baricitinib dose regimens (4-mg or 2-mg) and placebo in the 
proportion of patients achieving remission of arthritis and/or rash at Week 24 (Visit 9) will be 
analyzed using the logistic regression analysis with treatment and baseline disease activity 
(SLEDAI-2K <10 versus SLEDAI-2K ≥10), baseline anti-dsDNA status (positive; negative), and 
region in the model.  The proportions and 95% CI will be reported.  Missing data will be imputed 
using the NRI method.
9.4.2. Secondary Analyses 
Treatment comparison between baricitinib dose regimens (4-mg or 2-mg) and placebo for the
change from baseline in SLEDAI-2K score at Week 24, and the change from baseline in 
patient’s global assessment of disease activity at Week 24 will be analyzed using MMRM 
method with treatment, baseline disease activity (SLEDAI-2K <10 versus SLEDAI-2K ≥10), 
baseline anti-dsDNA status (positive; negative), region, visit, and the interaction of treatment-by-
visit as fixed factors.  An unstructured covariance matrix will be used  to model the within-
patient variance-covariance errors. Type III sums of squares for the LS means will be used for 
the statistical comparison; the 95% CI will also be reported. Treatment group comparisons with 
placebo at Week 24 and other visits will be tested.
Treatment comparison between baricitinib dose regimens (4-mg or 2-mg) and placebo for  the 
proportion of patients achieving a SRI-4 response and for the proportion of patients achieving a
reduction of ≥4 points in SLEDAI-2K score at Week 24 will be analyzed using the logistic 
regression model with treatment, baseline disease activity (SLEDAI-2K <10 versus SLEDAI-2K 
≥10), baseline anti-dsDNA status (positive; negative), and region in the model.  The proportions 
and 95% CI will be reported.  Missing data will be imputed using the NRI method.
9.4.3. Exploratory Analyses
Study JAHH exploratory analyses are summarized in Table JAHH.4.  Details of the exploratory 
analyses will be outlined in the SAP.

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Table JAHH.4.
Study JAHH Exploratory Analyses
Efficacy/Safety Measures
Variable
Analysis
SLEDAI-2K
Change in proportion of patients who achieve remission of 
arthritis and/or rash at Week 12
Logistic Regression
28 Tender/Swollen Joint 
Count
Change in number of joints affected by SLE arthritis at 
Week 12 and Week 24 compared to baseline
MMRM
Change in proportion of patients with ≥50% reduction in 
number of joints affected by SLE arthritis at Week 12 and 
Week 24 compared to baseline
Logistic Regression
CLASI Activity Score
Change at Week 12 and Week 24 compared to baseline
MMRM
Change in proportion of patients with ≥50% reduction at 
Week 12 and Week 24 compared to baseline
Logistic Regression
Physician Global Assessment 
of Disease Activity
Change at Week 12 and Week 24 compared to baseline
MMRM
SLEDAI Flare Index (SFI)
Proportion of patients experiencing severe, mild/moderate,
or any severity flare
Logistic Regression
Time to first severe, mild/moderate, or any severity flare
Kaplan-Meier 
Product Limit 
SLICC/ACR Damage Index 
Score
Change at Week 24 compared to baseline
MMRM
Corticosteroid Sparing 
Change in proportion of patients receiving ≥10mg/day 
prednisone at baseline able to reduce prednisone (or 
equivalent) dose ≤7.5 mg/day for 12 consecutive weeks 
between Week 12 and Week 24
Logistic Regression
Serologic Markers
The difference in reduction of IFN signature between 
treatment groups at Week 12 and Week 24 compared to 
baseline
MMRM
Change in anti-dsDNA level at Week 12 and Week 24 
compared to baseline in patients with elevated anti-dsDNA 
at baseline
MMRM
Change in C3 and C4 levels  at Week 12 and Week 24 
compared to baseline in patients with low C3 and C4 at 
baseline
MMRM
Abbreviations:  ACR = American College of Rheumatology; CLASI = Cutaneous Lupus Erythematosus Disease 
Area and Severity Index; dsDNA = double-stranded deoxyribonucleic acid; IFN = interferon; MMRM = mixed-
effects models for repeated measures; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus 
Erythematosus Disease Activity Index 2000; SLICC = Systemic Lupus Erythematosus International 
Collaborating Clinics.
Note:  Additional methods may be used for analysis as deemed appropriate.
9.5.
Safety Analyses
All safety data will be descriptively summarized by treatment groups and analyzed based on the 
mITT population. The safety analyses include AEs, laboratory analytes, QIDS-SR16, and vital
signs. The duration of dosing exposure will also be summarized.  For the Double-Blinded 
Treatment period, the safety data will be summarized and analyzed with pairwise comparisons 
between each baricitinib dose and placebo.  For the post-treatment Follow-Up Period, safety data 
will be summarized according to the dosing regimen to which they were assigned during the 

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treatment period.  The categorical safety measures will be summarized with incidence rates and 
analyzed by Fisher exact test. The mean change in the continuous safety measures of the vital 
signs, QIDS-SR16, physical characteristics, and laboratory values will be summarized by visits
and analyzed by ANCOVA with treatment and baseline values in the model. Other continuous
safety variables will be analyzed by t-tests, unless otherwise stated. Missing values will be 
imputed by modified last observation carried forward (mLOCF) for continuous vital signs and 
QIDS-SR16 safety variables.
9.5.1. Adverse Events
Adverse events are classified based upon the Medical Dictionary for Regulatory Activities 
(MedDRA).  An overall summary of AEs will be provided for the Double-Blinded Treatment 
Dosing Period.  Fisher exact test will be used to perform treatment comparisons between each 
baricitinib group and placebo.
Treatment-emergent adverse events (TEAEs) 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. TEAEs will also be 
summarized by relationship to investigational product and by severity within each treatment 
group.  Fisher exact test will be used to perform treatment comparisons between each baricitinib 
group and placebo.
SAEs including deaths, treatment-emergent AESIs, and AEs that lead to investigational product
discontinuation will also be summarized using MedDRA for each system organ class and each 
preferred term by treatment group.  Fisher exact test will be used to perform treatment 
comparisons between each baricitinib group and placebo.
A follow-up emergent adverse event (FEAE) is defined as an event that first occurred or 
worsened in severity after the date of the Week 24 visit (Visit 9) or the ETV.  Follow-up 
emergent AEs (all, by maximum severity, and FEAEs possibly related to investigational product
by the investigator) will be summarized by MedDRA system organ class and preferred term.
9.5.2. 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 by treatment group and analyzed using 
ANCOVA with treatment and baseline value in the model.  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.

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9.5.3. Vital Signs, Physical Findings, and Other Safety Evaluation
Observed values and changes from baseline (predose or screening if missing) for vital signs, 
QIDS-SR16, and physical characteristics will be descriptively summarized by treatment group 
and visit.
Change from baseline to postbaseline in vital signs, QIDS-SR16, and physical characteristics will 
be analyzed using ANCOVA with treatment and baseline value in the model.
9.6.
Pharmacokinetic/Pharmacodynamic Analyses
Sparse blood samples will be collected at selected visits for population PK analyses. PD 
endpoints will include both efficacy and safety measures including, but not limited to, for 
example, SLEDAI-2K, hemoglobin, and neutrophil count. Samples for inflammatory and 
exploratory biomarkers will also be collected.
PK data for baricitinib will be analyzed using a population approach via nonlinear mixed effects 
modeling (NONMEM) with the NONMEM software. PopPK parameters will be examined for 
relationships with dose, renal function, and patient factors including but not limited to age, 
weight, and sex.  Empirical Bayesian estimates of clearance will be used to calculate individual 
estimates of area under the plasma concentration-time curve (AUC).
Time-course models of the relationship between exposure and efficacy (SLEDAI-2K) as well as 
safety laboratory measures (such as hemoglobin and neutrophil counts) will be explored.  
Evaluations of covariate effects (such as age, sex, renal function, baseline values, and so on) on 
PK/PD relationships may also be evaluated.  Other exploratory analyses, such as the relationship 
between baricitinib exposure and biomarkers of pharmacologic activity, may be undertaken as 
deemed appropriate.
The relationship between dose/predicted concentrations and efficacy (such as SLEDAI-2K) and 
key safety markers (such as hematological endpoints) will be explored.
9.7.
Other Analyses
9.7.1. Health Outcomes
The analyses of health outcome measures include the Patient’s Global Assessment of Disease 
Activity, worst pain, worst joint pain, worst fatigue, and SF-36.  The categorical and continuous 
health outcome variables will be analyzed using logistic and MMRM methods, respectively.  The 
analyses will be based on the mITT population, unless otherwise specified.
More detailed analytical methods will be described in the SAP.
9.7.2. Subgroup Analyses.
Subgroup analysis may be conducted on the primary endpoint and selected secondary endpoints. 
Subgroups to be evaluated may include gender, age, race, disease severity, region, exploratory 
biomarkers, and background SoC therapy.  The definitions for the levels of the subgroup 

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variables and the analysis methodology will be provided in the SAP. Additional subgroup 
analyses may be performed as deemed appropriate.
9.8.
Interim Analyses
No interim analyses (IA) are planned for this study.  If an unplanned IA is deemed necessary, the 
appropriate Lilly medical director, or designee, will be consulted to determine whether it is 
necessary to amend the protocol. Adjustments to type I error will be made in case an unplanned 
IA for efficacy is performed.

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10. Study Governance Considerations
10.1. Regulatory and Ethical Considerations, Including the Informed 
Consent Process
10.1.1. Informed Consent
The investigator is responsible for ensuring:

that the patient understands the potential risks and benefits of participating in 
the study

that informed consent is given by each patient or legal representative.  This 
includes obtaining the appropriate signatures and dates on the 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 trial.
10.1.2. Ethical Review
The investigator must give assurance that the ERB was properly constituted and convened as 
required by International Conference on 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 GCP.
The study site’s ERB(s) should be provided with the following:

the current IB and updates during the course of the study

ICF

relevant curricula vitae.
10.1.3. Regulatory Considerations
This study will be conducted in accordance with:

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.

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10.1.4. 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 SLE may also 
participate as investigators. 
10.1.5. 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.
10.1.6. Final Report Signature
Lilly will select a qualified investigator(s) from among investigators participating in the design, 
conduct, and/or analysis of the study to serve as the CSR coordinating investigator.  If this 
investigator(s) is unable to fulfill this function, another investigator will be chosen by Lilly to 
serve as the CSR coordinating investigator.
The CSR coordinating investigator(s) 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.
10.2. 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 eCRFs, 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

review and evaluate eCRF 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 

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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.
10.2.1. 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 are entered into an ePRO 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 instrument record will serve as the source.
If ePRO 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 instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file.
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.
10.3. Study and Site Closure
10.3.1. Discontinuation of Study Sites
Study site participation may be discontinued if Lilly, 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.
10.3.2. Discontinuation of the Study
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP.

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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.
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANA
antinuclear antibody
ANC
absolute neutrophil count
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
BFI
Brief Fatigue Inventory
BPI
Brief Pain Inventory
BILAG
British Isles Lupus Assessment Group
blinding/masking
A double-blind study is one in which neither the patient 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.
BPI
Brief Pain Inventory
CI
confidence interval
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
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.
CNS
central nervous 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.

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CSR
clinical study report
dsDNA
double-stranded deoxyribonucleic acid
DN
diabetic nephropathy
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
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
ethical review board
ETV
early termination visit
FEAE
follow-up emergent adverse event
FSH
follicle-stimulating hormone
GCP
good clinical practice
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IA
interim analyses
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
IFN
interferon

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IM
intramuscular
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.
IRBs
investigational review boards
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.
IV
intravenous
IVIg
intravenous immunoglobulin
IWRS
interactive web-response system
JAK
Janus kinase
LLN
lower limit of normal
LLOQ
lower limit of quantification
LS means
least squares means
MCS
mental component score
MedDRA
Medical Dictionary for Regulatory Activities
MI
myocardial infarction
mITT
modified intent-to-treat 
MMRM
mixed-effects models for repeated measures
mRNA
messenger ribonucleic acid
MTX
methotrexate
NONMEM
nonlinear mixed effects modeling
NRI
nonresponder imputation
NRS
numeric rating scale
NSAIDs
nonsteroidal anti-inflammatory drugs

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PCS
physical component score
PD
pharmacodynamics(s)
PK
pharmacokinetic(s)
pMI
placebo multiple imputation
popPK/PD
population pharmacokinetics/pharmacodynamics
PPD
purified protein derivative
QD
daily
QIDS-SR16
Quick Inventory of Depressive Symptomatology Self-Rated–16
RA
rheumatoid arthritis
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
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-36
Short-Form 36-item health survey version 2
SFI
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
SLE Responder Index
STAT
signal transducer and activator of transcription
SUSARs
suspected unexpected serious adverse reactions
TB
tuberculosis
TBL
total bilirubin level
TEAE
treatment-emergent adverse event:  Any untoward medical occurrence that either occurs 
or worsens at any time after treatment baseline and that does not necessarily have to 
have a causal relationship with this treatment.
TSH
thyroid-stimulating hormone

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TYK
Tyrosine kinase
UACR
urinary albumin-to-creatinine ratio
ULN
upper limit of normal
WBC
white blood cells

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Appendix 2.
Schedule of Activities

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Schedule of Activities, Protocol I4V-MC-JAHH
Screening
Double-Blinded Treatment
Follow-Up
Visit Number
V1
V1aa
V2b
V3
V4
V5
V6
V7
V8
V9
ETc,d
V801d,e
Study Week
-6
0
2
4
8
12
16
20
24
any
28 or last dose
+ 4 weeks
Study Day
-42
to -3
1
15 ± 3
29 ± 4
57 ± 4
85 ± 4
113 ± 4
141 ± 4
169 ± 4
any
197 ± 5 or last dose 
+ 28  ± 5 days
Procedure 
Informed consent 
X
Medical history
X
Physical examination
X
Symptom-directed physical 
examination
X
X
X
X
X
X
X
X
X
X
Previous SLE therapy
X
X
Patient demographics
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
Waist circumference
X
X
X
X
Vital signs (BP, pulse, 
temperature)
X
X
X
X
X
X
X
X
X
X
X
Habitsf
X
ECGg
X
Inclusion/exclusion criteria 
review for entry
X
Inclusion/exclusion criteria 
review for enrollment
X
Administer TB testh
X
Read PPD test if used for TB 
testing
X
Chest x-rayi
X
Preexisting conditions
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X

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Screening
Double-Blinded Treatment
Follow-Up
Visit Number
V1
V1aa
V2b
V3
V4
V5
V6
V7
V8
V9
ETc,d
V801d,e
Study Week
-6
0
2
4
8
12
16
20
24
any
28 or last dose
+ 4 weeks
Study Day
-42
to -3
1
15 ± 3
29 ± 4
57 ± 4
85 ± 4
113 ± 4
141 ± 4
169 ± 4
any
197 ± 5 or last dose 
+ 28  ± 5 days
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
Randomization
X
Log in IWRS
X
X
X
X
X
X
X
X
X
X
X
Investigational product 
dispensed
X
X
X
X
X
X
X
Investigational product returned 
and compliance assessed
X
X
X
X
X
X
X
X
Clinical Efficacy
SLEDAI-2K
X
X
X
X
X
X
X
X
X
X
X
BILAG2004
X
X
X
X
X
X
X
X
X
X
SLEDAI Flare Index (SFI)
X
X
X
X
X
X
X
X
X
X
SLICC
X
X
X
CLASI
X
X
X
X
X
X
X
X
X
X
28-Tender and Swollen Joint 
counts
X
X
X
X
X
X
X
X
X
X
Physician’s Global Assessment 
of Disease Activity (VAS)
X
X
X
X
X
X
X
X
X
X
Patient’s Global Assessment of 
Disease Activity j
X
X
X
X
X
X
X
X
X
X
X
BPI (Worst Pain) j
X
X
X
X
X
X
X
X
X
X
X
BPI (Worst Joint Pain) j
X
X
X
X
X
X
X
X
X
X
X
BFI (Worst Fatigue) j
X
X
X
X
X
X
X
X
X
X
X
SF-36j
X
X
X
X
X
QIDS-SR16
j
X
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
TSH
X

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Screening
Double-Blinded Treatment
Follow-Up
Visit Number
V1
V1aa
V2b
V3
V4
V5
V6
V7
V8
V9
ETc,d
V801d,e
Study Week
-6
0
2
4
8
12
16
20
24
any
28 or last dose
+ 4 weeks
Study Day
-42
to -3
1
15 ± 3
29 ± 4
57 ± 4
85 ± 4
113 ± 4
141 ± 4
169 ± 4
any
197 ± 5 or last dose 
+ 28  ± 5 days
HIV
X
Hepatitis C antibody testing
X
Hepatitis B testing (HBsAg, 
HBcAb, HBsAb)
X
HBV DNAk
X
X
X
X
X
Serum pregnancy testl
X
X
Urine pregnancy testl
X
X
X
X
X
X
X
X
X
X
FSHm
X
Clinical chemistryn
X
X
X
X
X
X
X
X
X
X
X
Fasting lipid panelo
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
Iron studies (iron, TIBC, and 
ferritin)
X
X
X
hsCRP
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
ANA
X
X
X
anti-dsDNA
X
X
X
X
X
X
X
X
X
X
X
Autoantibodies (anti-Sm, anti-
RNP, anti-SSA/Ro, anti-
SSB/La)
X
X
X
Antiphospholipid antibodies
X
X
X
Complement (C3 and C4)
X
X
X
X
X
X
X
X
X
X
X
Immunoglobulins (IgG, IgA, 
IgM)
X
X
X
X
X
X
Lymphocyte subsets (T, B, NK, 
and T-cell subsets)
X
X
X
X
X
X

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Screening
Double-Blinded Treatment
Follow-Up
Visit Number
V1
V1aa
V2b
V3
V4
V5
V6
V7
V8
V9
ETc,d
V801d,e
Study Week
-6
0
2
4
8
12
16
20
24
any
28 or last dose
+ 4 weeks
Study Day
-42
to -3
1
15 ± 3
29 ± 4
57 ± 4
85 ± 4
113 ± 4
141 ± 4
169 ± 4
any
197 ± 5 or last dose 
+ 28  ± 5 days
Exploratory storage samples 
(serum and plasma)
X
X
X
X
Exploratory storage samples 
(urine)
X
X
X
X
Exploratory storage samples 
(RNA)
X
X
X
X
X
Baricitinib plasma 
concentrations (PK sample)
X p
X q
X r
X q
X s
Pharmacogenetic (DNA) 
collection
X
Abbreviations:  ANA = antinuclear antibody; BFI = Brief Fatigue Inventory; BILAG = British Isles Lupus Assessment Group; BP = blood pressure; BPI = Brief 
Pain Inventory; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; dsDNA = double-stranded deoxyribonucleic acid; ECG  = 
electrocardiogram; ET = early termination; FSH = follicle-stimulating hormone; HBV DNA = hepatitis B virus deoxyribonucleic acid; HBcAb = hepatitis B 
core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HIV = human immunodeficiency virus; hsCRP = high-sensitivity 
C-reactive protein; IWRS = interactive web-response system; PK = pharmacokinetics; PPD = purified protein derivative; QIDS-SR16 = Quick Inventory of 
Depressive Symptomatology Self-Rated-16; RNA = ribonucleic acid; SF-36 = Short-Form 36-item Health Survey; SLE = systemic lupus erythematosus; 
SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC = Systemic Lupus Erythematosus International Collaborating Clinics;
TB = tuberculosis; TIBC = total iron binding capacity; TSH = thyroid-stimulating hormone; V = visit; VAS = visual analog scale.
a
For those patients with a PPD placed at Visit 1, Visit 1a must occur 48 to 72 hours post-Visit 1 for PPD to be read. PPD 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.
b
All baseline assessments at Visit 2 must be performed and baseline laboratory samples must be drawn PRIOR to administration of the first dose of 
investigational product.
c
Those patients who discontinue from investigational product early should complete the ET visit and proceed to post-treatment follow-up. 
d
The ET visit can serve as Visit 801 if it occurs at least 28 days following the last dose of investigational product.
e
All patients should return for a post-treatment follow-up visit 28 days after the last dose of investigational product. 
f
Includes recording of habits such as caffeine, alcohol, and tobacco consumption.
g
ECGs will be performed locally and will be locally (machine) read.
h
If the PPD test results are 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 or T-SPOT.TB test (if available). If the QuantiFERON-TB Gold or T-SPOT.TB test results are not negative, the patient will be 

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considered to have latent TB. If the QuantiFERON-TB Gold or T-SPOT.TB test is available and, in the judgment of the investigator, is preferred as an 
alternative to the PPD skin test for the evaluation of TB infection, it may be used instead of the PPD TB test. If the QuantiFERON-TB Gold or TSPOT.TB 
test is positive, the patient will be considered to have latent TB. If the test is not negative, the test may be repeated once within 2 weeks of the initial value. If 
the repeat test results are again not negative, the patient will be considered to have latent TB.
i
A chest x-ray will be taken at screening unless one has been obtained within 6 months prior to the study (provided the x-ray and/or report are available for 
review).
j
Patient-reported questionnaires will be administered via an electronic patient-reported outcomes (ePRO) device and should be administered prior to any 
clinical assessments.
k
HBV DNA testing will be performed in patients who tested positive for HBcAb at screening. Patients who are HBcAb positive and HBV DNA negative at 
Visit 1 will require HBV DNA monitoring every 3 months, at an ET visit, and at Visit 801, regardless of their HBsAb status. If the HBV DNA result is above 
the lower limit of quantification (LLOQ), refer to Section 7.1.2 and Section 8.4.4. For study sites in Japan (or elsewhere if required), if a patient is HBcAb 
positive and/or HBsAb positive and negative for HBV DNA at Visit 1, HBV DNA needs to be checked at least monthly and at the patient’s last visit.
l
For all women of childbearing potential, a serum pregnancy test (central laboratory) will be performed at Visits 1 and 2. Urine pregnancy tests (local 
laboratory) will also be performed at Visit 2 and at all subsequent study visits.
m To confirm postmenopausal status for women ≥40 and <60 years of age who have had a cessation of menses, an FSH test will be performed. Nonchildbearing 
potential is defined as an FSH ≥40 mIU/mL and a cessation of menses for at least 12 months.
n
Clinical chemistry will include the following values calculated from serum creatinine:  estimated glomerular filtration rate (eGFR; calculated using the 
Modification of Diet in Renal Disease [MDRD] isotope dilution mass spectrometry traceable method).
o
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, this will not be considered a protocol violation.
p
At Visit 2, one PK sample will be collected 15 to 30 minutes POSTdose, as described in Section 8.5. Apart from this single PK sample, all other baseline 
laboratory samples are taken PREdose.
q
A single PK sample will be collected at Visit 4 and Visit 7 at any time predose, as described in Section 8.5. To reduce the number of blood draws, the predose 
PK sample may be drawn at the same time as other labs required at the visit. If a patient arrives at the clinic on Visit 4 or Visit 7 after having taken the dose, 
the PK sample should be drawn with other routine labs randomly at any time postdose.
r
A single PK sample will be collected at Visit 5 between 1 and 3 hours postdose, as described in Section 8.5. To reduce the number of blood draws, the 
postdose PK sample may be drawn at the same time as other routine labs required at the visit.  
s
A single PK sample is to be collected, if possible, from patients who discontinue the study early. In the event of a serious adverse event (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.

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Appendix 3.
Clinical Laboratory Tests

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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 cell hemoglobin (MCH)
Alkaline phosphatase (ALP)
Mean cell hemoglobin concentration (MCHC) 
Leukocytes (WBC)
Alanine aminotransaminase (ALT)/serum glutamic 
pyruvic transaminase
Absolute count of 
Neutrophils, segmented
Aspartate aminotransferase (AST)/serum glutamic 
oxaloacetic transaminase 
Neutrophils, juvenile (bands)
Blood urea nitrogen (BUN)
Lymphocytes
Creatinine
Monocytes
Estimated glomerular filtration rate (eGFR)c
Eosinophils
Uric acid
Basophils
Calcium
Platelets
Glucosed
Cell morphology
Albumin
Differential and blood smeare
Creatine phosphokinase (CPK)
Total protein
Iron studies (iron, TIBC, and ferritin)
Lymphocyte subsets (T, B, NK, and T-cell subsets) Lipid Profiled,f
Total cholesterol
Urinalysisb
High-density lipoprotein cholesterol (HDL-C)
Color
Low-density lipoprotein cholesterol (LDL-C)
Specific gravity
Triglycerides
pH
Protein
Other Tests
Glucose
Serum pregnancy test (females only)g
Ketones
Urine pregnancy test (females only)g
Blood
Follicle-stimulating hormone (FSH) (females only)h
Bilirubin
Hepatitis B surface antigen (HBsAg)
Urobilinogen
Hepatitis B surface antibody (HBsAb)
Leukocyte esterase
Hepatitis B core antibody (HBcAb)
Nitrite
Hepatitis C antibodyi
Urine creatinine
HBV DNAk
Microscopic examination of sedimentj
Human immunodeficiency virus (HIV) serology
PPD or QuantiFERON®-TB Gold, or T-SPOT®.TBl
Anti-nuclear antibody (ANA)
Thyroid-stimulating hormone (TSH)
Anti-double-stranded DNA (anti-dsDNA) antibody High-sensitivity C-reactive protein (hsCRP)
Autoantibodies (anti-RNP, anti-Sm, anti-SSA/Ro, 
anti-SSB/La)
Stored serum, plasma, urine, mRNAm, and DNA 
samples for exploratory biomarker analyses
Antiphospholipid antibodies 
Serum immunoglobulins (IgG, IgA, IgM)
Complement C3 and C4
Baricitinib plasma concentration (PK sample)
Abbreviations:  HBV DNA = hepatitis B virus deoxyribonucleic acid; 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.

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b
Unscheduled blood chemistry (including CPK), hematology, and urinalysis panels may be performed at the 
discretion of the investigator. If tests are done to evaluate laboratory results to resume investigational product, 
samples must be assayed centrally.
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, Week 12, and Week 24. If a patient 
attends these visits in a nonfasting state, this will not be considered a protocol violation. These tests may be 
performed nonfasting at all other visits.
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 childbearing potential, a serum pregnancy test (central laboratory) will be performed at Visit 1, 
and both urine (local laboratory) and serum pregnancy (central laboratory) tests will be performed at Visit 2 to 
determine study eligibility. Urine pregnancy tests (local laboratory) will also be performed at each subsequent 
study visit per the Schedule of Activities.
h
To confirm postmenopausal status for women ≥40 and <60 years of age, an FSH test will be performed. 
Nonchildbearing potential is defined as an FSH ≥40 mIU/mL and a cessation of menses for at least 12 months. 
i
A positive hepatitis C antibody result will be confirmed with a positive hepatitis C virus result.
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. Patients who are 
HBcAb positive and HBV DNA negative at Visit 1 will require HBV DNA monitoring every 3 months, at an 
early termination (ET) visit, and at Visit 801, regardless of their HBsAb status. If the HBV DNA result is above 
the lower limit of quantification (LLOQ), refer to Section 7.1.2 and Section 8.4.4. For study sites in Japan (or 
elsewhere if required), if a patient is HBcAb positive and/or HBsAb positive and negative for HBV DNA at 
Visit 1, HBV DNA needs to be checked at least monthly and at the patient’s last visit.
l
PPD, QuantiFERON®-TB Gold, and T-SPOT®.TB tests may be performed locally. Test will be required at Visit 
1 only to determine eligibility of patient for the study. In countries where the QuantiFERON-TB Gold or T-
SPOT.TB test is available and, in the judgment of the investigator, medically preferred as an alternative to the 
PPD test for the evaluation of mycobacterium tuberculosis (MTB) infection, either may be used instead of the 
PPD test (positive tests excluded).
m Interferon (IFN) signature will be assayed from stored mRNA sample.

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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, CRP.
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
ALP
ALT
Anti-Nuclear Antibody (ANA)a
AST
GGT
Alkaline Phosphatase Isoenzymesa
CPK
Anti-Smooth Muscle Antibody (or anti-actin 
antibody)a
Abbreviations:  ALP = alkaline phosphatase; 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.

Leo Document ID = 4a1b1699-ff86-4f60-85c4-c62821a732f9
Approver: 
Approval Date & Time: 11-Dec-2015 20:06:16 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 11-Dec-2015 20:41:38 GMT
Signature meaning: Approved
PPD
PPD