A Phase 3, Double-Blind, Multicenter Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Patients With Systemic Lupus Erythematosus (SLE)
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Sponsor: Eli Lilly and Company

 
 
 
Protocol I4V-MC-JAIM(a) 
 
 
A Phase 3, Double-Blind, Multicenter Study to Evaluate the Long-Term Safety and Efficacy of 
Baricitinib in Patients with Systemic Lupus Erythematosus (SLE) 
  
 
NCT03843125 
 
Approval Date: 15-Nov-2019 
 
 
 
 
 
 

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Approval Date: 15-Nov-2019 GMT
Protocol I4V-MC-JAIM(a)
A Phase 3, Double-Blind, Multicenter Study to Evaluate the 
Long-Term Safety and Efficacy of Baricitinib in Patients 
with Systemic Lupus Erythematosus (SLE)
EUDRA CTA 2017-005028-11
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
baricitinib (LY3009104), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure. Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release. In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Baricitinib (LY3009104)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly on 29-Jun-2018.
Amendment (a) Electronically Signed and Approved by Lilly
on approval date provided below.

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Table of Contents
Section
Page
Protocol I4V-MC-JAIM(a) A Phase 3, Double-Blind, Multicenter Study to 
Evaluate the Long-Term Safety and Efficacy of Baricitinib in 
Patients with Systemic Lupus Erythematosus (SLE)............................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................13
3.
Introduction ......................................................................................................................20
3.1.
Study Rationale............................................................................................................20
3.2.
Background..................................................................................................................21
3.3.
Benefit/Risk Assessment..............................................................................................22
3.4.
Scientific Rationale for Study Design...........................................................................24
4.
Objectives and Endpoints..................................................................................................25
5.
Study Design.....................................................................................................................27
5.1.
Overall Design .............................................................................................................27
5.2.
Number of Participants.................................................................................................28
5.3.
End of Study Definition ...............................................................................................28
5.4.
Justification for Dose ...................................................................................................28
6.
Study Population...............................................................................................................30
6.1.
Inclusion Criteria..........................................................................................................30
6.2.
Exclusion Criteria ........................................................................................................32
6.3.
Lifestyle Restrictions....................................................................................................32
6.4.
Screen Failures.............................................................................................................32
7.
Treatments........................................................................................................................33
7.1.
Treatments Administered .............................................................................................33
7.1.1.
Packaging and Labelling ......................................................................................33
7.2.
Method of Treatment Assignment ................................................................................34
7.2.1.
Selection and Timing of Doses.............................................................................34
7.2.2.
Dose Adjustment for Renal Impairment ...............................................................34
7.3.
Blinding .......................................................................................................................35
7.4.
Dosage Modification....................................................................................................35
7.5.
Preparation/Handling/Storage/Accountability...............................................................35
7.6.
Treatment Compliance .................................................................................................36
7.7.
Concomitant Therapy...................................................................................................36
7.8.
Treatment after the End of the Study............................................................................37

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7.8.1.
Treatment after Study Completion........................................................................37
8.
Discontinuation Criteria ....................................................................................................38
8.1.
Discontinuation from Study Treatment.........................................................................38
8.1.1.
Temporary Interruption of Investigational Product ...............................................38
8.1.2.
Permanent Discontinuation from Study Treatment ...............................................39
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................40
8.2.
Discontinuation from the Study....................................................................................40
8.3.
Lost to Follow-Up........................................................................................................41
9.
Study Assessments and Procedures ...................................................................................42
9.1.
Efficacy Assessments...................................................................................................42
9.1.1.
Secondary Efficacy Assessments..........................................................................42
9.1.1.1.
Systemic Lupus Responder Index ...................................................................42
9.1.1.2.
Systemic Lupus Erythematosus Disease Activity 
Index-2000 .....................................................................................................42
9.1.1.3.
British Isles Lupus Assessment Group 2004 Index..........................................42
9.1.1.4.
Physician’s Global Assessment of Disease Activity........................................43
9.1.1.5.
Systemic Lupus Erythematosus Responder Index ...........................................43
9.1.1.6.
Safety of Estrogens in Lupus Erythematosus National 
Assessment (SELENA)-Systemic Lupus Erythematosus 
Disease Activity Index (SLEDAI) Flare Index................................................43
9.1.1.7.
Cutaneous Lupus Erythematosus Disease Area and 
Severity Index ................................................................................................43
9.1.1.8.
Lupus Low Disease Activity State..................................................................43
9.1.1.9.
Tender/Swollen Joint Count (28 Joints) ..........................................................44
9.1.1.10.
Systemic Lupus International Collaborating 
Clinics/American College of Rheumatology Damage 
Index ..............................................................................................................44
9.1.1.11.
Health Outcomes and Quality of Life Measures..............................................44
9.1.1.11.1.
Worst Pain Numeric Rating Scale.............................................................44
9.1.1.11.2.
Worst Joint Pain Numeric Rating Scale.....................................................44
9.1.1.11.3.
Worst Fatigue Numeric Rating Scale ........................................................44
9.1.1.11.4.
Patient’s Global Impression of Severity ....................................................44
9.1.1.11.5.
Medical Outcomes Short-Form 36-Item Health 
Survey Version 2 (SF-36v2) .....................................................................45
9.1.1.11.6.
Functional Assessment of Chronic Illness Therapy–
Fatigue Scale ............................................................................................45
9.1.1.11.7.
Work Productivity and Activity Impairment 
Questionnaire–Lupus ................................................................................45
9.1.1.11.8.
European Quality of Life-5 Dimensions-5 Levels .....................................45
9.1.2.
Appropriateness of Assessments ..........................................................................46

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9.2.
Adverse Events ............................................................................................................46
9.2.1.
Serious Adverse Events........................................................................................47
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................47
9.2.2.
Adverse Events of Special Interest .......................................................................48
9.2.3.
Complaint Handling.............................................................................................48
9.3.
Treatment of Overdose.................................................................................................48
9.4.
Safety...........................................................................................................................48
9.4.1.
Vital Signs ...........................................................................................................48
9.4.2.
Physical Examination...........................................................................................49
9.4.3.
Laboratory Tests ..................................................................................................49
9.4.4.
Columbia-Suicide Severity Rating Scale ..............................................................49
9.4.5.
16-Item Quick Inventory of Depressive Symptomatology-
Self Report...........................................................................................................49
9.4.6.
Hepatitis B Virus (HBV) DNA Monitoring ..........................................................50
9.4.7.
Hepatic Safety Monitoring ...................................................................................50
9.4.8.
Safety Monitoring ................................................................................................51
9.4.9.
Venous Thromboembolic Events..........................................................................51
9.5.
Pharmacokinetics .........................................................................................................52
9.6.
Pharmacodynamics ......................................................................................................52
9.7.
Pharmacogenomics ......................................................................................................52
9.7.1.
Whole Blood Samples for Pharmacogenetic Research..........................................52
9.8.
Biomarkers...................................................................................................................52
9.9.
Medical Resource Utilization and Health Economics ...................................................52
10.
Statistical Considerations ..................................................................................................53
10.1. Sample Size Determination ..........................................................................................53
10.2. Populations for Analyses..............................................................................................53
10.3. Statistical Analyses ......................................................................................................53
10.3.1.
General Statistical Considerations ........................................................................53
10.3.2.
Treatment Group Comparability...........................................................................54
10.3.2.1.
Patient Disposition..........................................................................................54
10.3.2.2.
Patient Characteristics ....................................................................................54
10.3.2.3.
Concomitant Therapy .....................................................................................54
10.3.2.4.
Treatment Compliance....................................................................................54
10.3.3.
Efficacy Analyses ................................................................................................54
10.3.3.1.
Missing Data Imputation ................................................................................55
10.3.4.
Safety Analyses....................................................................................................55
10.3.4.1.
Adverse Events...............................................................................................55
10.3.4.2.
Clinical Laboratory Tests................................................................................56

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10.3.4.3.
Vital Signs, Physical Findings, and Other Safety 
Evaluation ......................................................................................................56
10.3.5.
Subgroup Analyses ..............................................................................................56
10.3.6.
Interim Analyses..................................................................................................56
11.
References ........................................................................................................................57
12.
Appendices .......................................................................................................................61

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List of Tables
Table
Page
Table JAIM.1.
Schedule of Activities....................................................................................14
Table JAIM.2.
Objectives and Endpoints...............................................................................25
Table JAIM.3.
Treatment Regimens......................................................................................33
Table JAIM.4.
Criteria for Temporary Interruption of Investigational Product.......................38

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List of Figures
Figure
Page
Figure JAIM.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIM....................28

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................62
Appendix 2.
Clinical Laboratory Tests...............................................................................66
Appendix 3.
Study Governance Considerations..................................................................68
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................73
Appendix 5.
Monitoring Tests for Confirmed VTE............................................................74
Appendix 6.
Protocol Amendment I4V-MC-JAIM (a) Summary - A Phase 3, 
Double-Blind, Multicenter Study to Evaluate the Long-Term Safety and 
Efficacy of Baricitinib in Patients with Systemic Lupus Erythematosus 
(SLE).............................................................................................................75

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

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Objective(s)/Endpoints:
Objectives
Endpoints
Primary
To evaluate the long-term safety and tolerability of 
baricitinib in patients with SLE.
Safety and tolerability assessments will include: 

Proportion of patients with treatment-emergent 
adverse events (TEAEs), adverse events of special 
interest (AESIs), and serious adverse events (SAEs).

Proportion of patients with temporary 
investigational product interruptions and permanent 
discontinuations.
Secondary

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD and background standard-of-care 
therapy on SLE disease activity. 

Proportion of patients achieving SRI-4 response
through Week 156, defined as:
o Reduction of  ≥4 points from baseline in 
SLEDAI-2K score; and
o No new British Isles Lupus Assessment Group 
(BILAG) A or no more than 1 new BILAG B 
disease activity score; 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.

Proportion of patients achieving an SRI-5, -6, -7, or 
-8 response through Week 156.

Proportion of patients achieving an LLDAS 
response through Week 156.

Change from baseline in mean total SLEDAI-2K 
scores through Week 156.

Change from baseline in Physician’s Global Disease 
Activity score through Week 156.

To evaluate the long-term corticosteroid sparing 
effect of baricitinib 4-mg or 2-mg QD.

Change from baseline in prednisone dose through 
Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on SLE flares.

Annualized mild/moderate flare rate.

Annualized severe flare rate.

Annualized flare rate (any severity).

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on mucocutaneous manifestations of 
SLE.

Proportion of patients with CLASI total activity 
score ≥10 at baseline with ≥50% reduction in 
CLASI total activity score through Week 156.

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Objective(s)/Endpoints:
Objectives
Endpoints

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on musculoskeletal manifestations of 
SLE.

Change from baseline in tender joint count through 
Week 156.

Change from baseline in swollen joint count through 
Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on individual organ system disease 
activity.

Proportion of patients with improvement in each 
SLEDAI-2K organ system versus baseline through 
Week 156.

Proportion of patients with worsening in each 
SLEDAI-2K organ system versus baseline through 
Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on damage.

Change from baseline in SLICC/ACR damage index 
total score through Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on patient-reported outcomes (PROs).

Change from baseline in Worst Pain NRS through 
Week 156.

Change from baseline in Worst Joint Pain NRS 
through Week 156.

Change from baseline in Worst Fatigue NRS 
through Week 156.

Change from baseline in Patient Global Impression 
of Severity through Week 156. 

Change from baseline in mental component score 
(MCS), physical component score (PCS), and 
domain scores in the Short-Form 36-item health 
survey version 2 (SF- 36v2) acute through Week 
156.

Change from baseline in FACIT-F total score
through Week 156.

Change from baseline in the EQ-5D-5L through 
Week 156.

Change from baseline in the WPAI-Lupus through 
Week 156.
Abbreviations:  CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; EQ-5D-5L = 5-level 
EuroQol-5 Dimensions; FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; 
LLDAS = Lupus Low Disease Activity State; NRS = Numeric Rating Scale; QD = once daily; SLE = systemic 
lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; 
SLICC/ACR = Systemic Lupus Erythematosus International Collaborating Clinics/American College of 
Rheumatology; SRI-4 = Systemic Lupus Erythematosus Responder Index-4; WPAI = Work Productivity and 
Activity Impairment. 

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Summary of Study Design:
Study I4V-MC-JAIM [JAIM] is a Phase 3, multicenter, randomized, outpatient, long term
extension trial to evaluate the long-term safety and efficacy of baricitinib in eligible patients with 
SLE who have completed the treatment period in an originating study (such as, 
Study I4V-MC-JAHZ [JAHZ] or Study I4V-MC-JAIA [JAIA]). 
Treatment Arms and Duration:
Patients randomized to active treatment, baricitinib 4-mg daily or baricitinib 2-mg daily, during 
Study JAHZ or Study JAIA will continue on the same, blinded, dose of baricitinib in Study 
JAIM.  Patients randomized to placebo during Study JAHZ or Study JAIA will be randomized 
1:1 to receive baricitinib 4-mg or baricitinib 2-mg daily during Study JAIM.  The treatment 
period will last up to 156 weeks (3 years) from enrollment into Study JAIM.
Number of Patients:
The study will enroll approximately 1100 patients.
Statistical Analysis:
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the 
modified intent-to-treat population, which includes patients who received at least 1 dose of 
investigational product in Study JAIM.  Safety analyses for JAIM will be conducted on those 
patients who receive at least 1 dose of investigational product in JAIM who do not discontinue at 
the first post-baseline visit of JAIM for the reason "Lost to Follow-up".
Efficacy and health outcomes analyses will generally be summarized using descriptive statistics.  
The number and percentage of patients maintaining or achieving a categorical efficacy or health 
outcomes response will be summarized.  The mean changes of the continuous measures will be 
summarized using mixed model repeated measures.  The model will include treatment, region, 
visit, treatment-by-visit interaction as fixed categorical effects, and baseline value and baseline 
value-by-visit interaction as fixed continuous effects to estimate change from baseline across 
postbaseline visits. Missing data will be imputed at specified time points utilizing methodologies, 
including last observation carried forward and nonresponder imputation. 
All safety data will be descriptively summarized by treatment group and analyzed using the 
safety population. Safety assessments will include adverse events, laboratory analytes, vital 
signs, and questionnaires to assess the existence and severity of depression. Some of the safety 
endpoints may be better assessed in the context of combining the safety data from the originating 
studies.  These details will be included in the statistical analysis plan (SAP) for this study or the 
integrated SAP (which will detail how all Phase 2 and 3 studies will be combined).
The categorical safety measures will be summarized with percentages and incidence rates, where 
appropriate.  The mean changes of the continuous safety measures will be summarized using 
descriptive statistics.

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2. Schedule of Activities

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Table JAIM.1.
Schedule of Activities
Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W84
W108
W132
W156
Any
W160 or last 
dose + 4 weeks
Study Day
1
29 ± 4
85 ± 7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
589 
± 14
757
± 14
925
± 14
1093 
± 14
Any
Last dose + 28 
± 5 days
Procedure
Informed consent
X
Abbreviated patient 
demographics
X
Symptom-directed 
physical examination
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Weight
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Waist circumference  
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BPd, 
pulse, temperature)
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Review JAIM 
inclusion/exclusion 
criteria 
X
Adverse events
Xe
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications
Xf
X
X
X
X
X
X
X
X
X
X
X
X
C-SSRSg & Self-
Harm Supplement 
Form
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up 
Formh
Xc
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16 i
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Log in IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomizationj
X

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Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W84
W108
W132
W156
Any
W160 or last 
dose + 4 weeks
Study Day
1
29 ± 4
85 ± 7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
589 
± 14
757
± 14
925
± 14
1093 
± 14
Any
Last dose + 28 
± 5 days
Investigational 
product dispensed
X
X
X
X
X
X
X
X
X
Investigational 
product returned and 
compliance assessed
Xk
X
X
X
X
X
X
X
X
X
X
Physician-Completed Scalesl
SLEDAI-2K
Xc
X
X
X
X
X
X
X
X
X
X
X
X
BILAG2004
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment of 
Disease Activity
Xc
X
X
X
X
X
X
X
X
X
X
X
X
SLEDAI Flare Index
Xc
X
X
X
X
X
X
X
X
X
X
X
X
SLICC/ACR
Damage Index
Xc
X
X
X
CLASI
Xc
X
X
X
X
X
X
X
X
28-Tender and 
Swollen Joint Counts
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Patient-Reported Questionnaires
Worst Pain NRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Joint Pain 
NRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Fatigue NRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Impression of 
Severity (PGI-S)i
X
X
X
X
X
X
X
X
X
X
X
X
X
SF-36v2i
Xc
X
X
X
X
X
X
X
X
X
X
X
X
FACIT-Fatiguei
Xc
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAIM(a) Clinical Protocol
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Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W84
W108
W132
W156
Any
W160 or last 
dose + 4 weeks
Study Day
1
29 ± 4
85 ± 7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
589 
± 14
757
± 14
925
± 14
1093 
± 14
Any
Last dose + 28 
± 5 days
WPAI-Lupusi
Xc
X
X
X
X
X
X
X
X
X
X
X
X
EQ-5D-5Li
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
HBV DNAm
Xc
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy 
testn
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Clinical chemistryo
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Fasting lipid panelp
Xc
X
X
X
X
X
Hematology
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Urine Creatinine and 
Protein, Ratio
Xc
X
X
X
X
X
X
X
X
X
X
X
X
ANA
Xc
X
X
Anti-dsDNA
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Autoantibodies (anti-
Smith, anti-RNP, 
anti-SSA/Ro, anti-
SSB/La)
Xc
X
X
Anti-cardiolipin 
antibodies IgG, IgA, 
IgM)
Xc
X
X
X
X
Anti-beta2 
glycoprotein-I (IgG, 
IgM) 
Xc
X
X
X
X
Lupus anticoagulant 
(dRVVT)
Xc
X
X
X
X

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Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W84
W108
W132
W156
Any
W160 or last 
dose + 4 weeks
Study Day
1
29 ± 4
85 ± 7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
589 
± 14
757
± 14
925
± 14
1093 
± 14
Any
Last dose + 28 
± 5 days
Complement (C3 and 
C4)
Xc
X
X
X
X
X
X
X
X
X
X
X
X
Immunoglobulins 
(IgG, IgA, IgM)
Xc
X
X
X
X
Exploratory storage 
samples (serum and 
plasma)
Xc
X
X
Exploratory storage 
samples (urine)
Xc
X
X

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Abbreviations:  ANA = antinuclear antibody; BILAG = British Isles Lupus Assessment Group; BP = blood pressure; CLASI = Cutaneous Lupus Erythematosus 
Disease Area and Severity Index; C-SSRS = Columbia-Suicide Severity Rating Scale; dRVVT = Dilute Russell’s Viper Venom Time; dsDNA = double-
stranded deoxyribonucleic acid; EQ-5D-5L = 5-level EuroQol-5 Dimensions; ET = early termination; FACIT = Functional Assessment of Chronic Illness 
Therapy; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBV DNA = hepatitis B virus deoxyribonucleic acid; 
Ig = immunoglobulin; IWRS = interactive web-response system; NRS = numerical rating scale; PGI-S = Patient’s Global Impression of Severity; 
RNP = ribonucleoprotein; QIDS-SR16  =16-Item Quick Inventory of Depressive Symptomatology-Self Report; SF-36v2 = Short-Form 36-item Health Survey
version 2; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC/ACR = Systemic Lupus 
Erythematosus International Collaborating Clinics/American College of Rheumatology; SSA/Ro = Sjögren’s-Syndrome-related antigen A; SSB/La = Sjögren
syndrome type B antigen/Lupus La protein; V = visit; W = week; WPAI = Work Productivity and Activity Impairment.
a
Patients who discontinue from investigational product (IP) early should complete the ET visit and proceed to post-treatment follow-up.
b
All patients should return for Visit 801, a post-treatment follow-up visit, 28±5 days after the last dose of IP. Patients who discontinue IP but remain in the 
study for at least 28±5 days without IP, can combine their Visit 11/ET with their Visit 801 (post-treatment follow-up visit).
c
Visit 1 of Study JAIM should occur on the same day as the final visit of the originating study.  Assessments/procedures required for both Visit 1 of Study 
JAIM and the final visit of the origination study should only be performed once.
d
At each time point, 3 replicate readings should be made at approximately 30- to 60-second intervals. Blood pressure is recorded as the average of these 3
readings. A single pulse measurement should be made simultaneously with at least 1 of the readings at each time point (Section 9.4.1. for details on vital 
signs).
e
Adverse events that are ongoing at the completion of the originating trial should be reported as pre-existing conditions at Visit 1 for Study JAIM. 
f
Concomitant medications ongoing at the completion of the originating trial should be reported as concomitant medications at Visit 1 for Study JAIM.
g
Suicidal ideation and behavior subscales excerpt; adapted for the assessment of 11 preferred ideation and behavior categories.  C-SSRS and Self-Harm 
Supplemental Form should be completed after collection of unsolicited adverse events.
h
The Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form.
i
Patient-reported questionnaires will be administered via an on-site electronic clinical outcome assessment (eCOA) device and should be administered prior to 
any clinical assessments.  
j
At Visit 1, patients randomized to active treatment during the originating study will be assigned to the same, blinded dose of baricitinib in Study JAIM.  
Patients randomized to placebo during the originating study will be randomized 1:1 to blinded baricitinib 2-mg or baricitinib 4-mg.  Dose adjustment for 
patients newly randomized to baricitinib, if necessary, will be based on the last available estimated glomerular filtration rate (eGFR) from the originating 
study.
k
New bottles of study drug tablets will NOT be dispensed at Week 4 (Visit 2) unless the patient requires additional tablets for the next visit window.  Patients 
will continue to take tablets from the bottles dispensed at Week 0 (Visit 1).  Compliance will be checked, and the bottles with remaining tablets will be 
returned to the patient for dosing the following visit window.  If new bottles are required, the patient will not have their previous bottles returned.
l
SLE assessments must be completed by a physician and will be documented on an eCOA (electronic clinical outcome assessment) device.
m Patients who were enrolled in the originating study with positive HBcAb and negative HBV DNA, regardless of HBsAb status or level, must undergo HBV 
DNA testing per the schedule of events (see Section 9.4.6 for details of HBV DNA monitoring).

I4V-MC-JAIM(a) Clinical Protocol
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n
For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at all study visits.  If required per local regulations and/or 
institutional guidelines, pregnancy testing can occur more frequently during the study treatment period.  Unscheduled urine pregnancy tests may also be 
performed if a regular monthly menstruation is absent in a woman of childbearing potential. 
o
Clinical chemistry will include the following value calculated from serum creatinine:  eGFR (calculated using the Modification of Diet in Renal Disease 
[MDRD] isotope dilution mass spectrometry traceable method).
p
Patients should not eat or drink anything, except water, for 12 hours prior to sample collection. If a patient attends these visits in a nonfasting state, the 
sample should still be collected.  This will not be considered a protocol violation.

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

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

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

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

I4V-MC-JAIM(a) Clinical Protocol
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establish a causal association.  With long-term exposures, the exposure-adjusted incidence rate of 
VTE for baricitinib-treated patients with RA was similar to the background rates published in the 
literature for the target population.  There was no pattern of increased or decreased risk with
continuing, long-term exposures, and cases observed with baricitinib were confounded by one or 
more recognized risk factors for VTE.  Venous thromboembolic event risk can be managed 
through risk mitigation strategies.  Exclusion and discontinuation criteria have been included in 
this protocol and the originating study protocols to limit participation of patients who are at an 
increased risk of VTE.
In the context of the cumulative knowledge, the benefit/risk balance for baricitinib in the 
treatment of adult patients with SLE is assessed to be favorable.
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated adverse events (AEs) of baricitinib are to be found in the Investigator’s Brochure 
(IB).
3.4.
Scientific Rationale for Study Design
Study JAIM is a long-term extension study for patients who complete the treatment period of an 
originating study, such as Study JAHZ or JAIA.  The primary intent of Study JAIM is to 
evaluate safety associated with long-term exposure to baricitinib.  The absence of a placebo arm 
in Study JAIM is consistent with other studies evaluating the long-term safety of investigational 
drugs in patients with SLE.
Background concomitant SoC therapy, including corticosteroids, antimalarials, and
immunosuppressants are permitted during the study.
Safety assessments will be based on the total duration of baricitinib exposure, including exposure 
during the originating study.  Efficacy assessments will also use disease severity measures 
obtained at the time of initial randomization in the originating study as baseline values.

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4.
Objectives and Endpoints
Table JAIM.2 shows the objectives and endpoints of the study.
Table JAIM.2.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the long-term safety and tolerability of 
baricitinib in patients with SLE.
Safety and tolerability assessments will include: 

Proportion of patients with treatment-emergent 
adverse events (TEAEs), adverse events of special 
interest (AESIs), and serious adverse events (SAEs).

Proportion of patients with temporary 
investigational product interruptions and permanent 
discontinuations.
Secondary

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD and background standard-of-care 
therapy on SLE disease activity. 

Proportion of patients achieving SRI-4 response
through Week 156, defined as:
o Reduction of ≥4 points from baseline in 
SLEDAI-2K score; and
o No new British Isles Lupus Assessment Group 
(BILAG) A or no more than 1 new BILAG B 
disease activity score; 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.

Proportion of patients achieving an SRI-5, -6, -7, or 
-8 response through Week 156.

Proportion of patients achieving an LLDAS 
response through Week 156.

Change from baseline in mean total SLEDAI-2K 
scores through Week 156.

Change from baseline in Physician’s Global Disease 
Activity score through Week 156.

To evaluate the long-term corticosteroid sparing 
effect of baricitinib 4-mg or 2-mg QD.

Change from baseline in prednisone dose through 
Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on SLE flares.

Annualized mild/moderate flare rate

Annualized severe flare rate

Annualized flare rate (any severity). 

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Objectives and Endpoints
Objectives
Endpoints

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on mucocutaneous manifestations of 
SLE.

Proportion of patients with CLASI total activity 
score ≥ 10 at baseline with ≥50% reduction in 
CLASI total activity score through Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on musculoskeletal manifestations of 
SLE.

Change from baseline in tender joint count through 
Week 156.

Change from baseline in swollen joint count through 
Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on individual organ system disease 
activity.

Proportion of patients with improvement in each 
SLEDAI-2K organ system versus baseline through 
Week 156.

Proportion of patients with worsening in each 
SLEDAI-2K organ system versus baseline through 
Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on damage.

Change from baseline in SLICC/ACR damage index 
total score through Week 156.

To evaluate the long-term effect of baricitinib 4-mg 
or 2-mg QD on patient-reported outcomes (PROs).

Change from baseline in Worst Pain NRS through 
Week 156.

Change from baseline in Worst Joint Pain NRS 
through Week 156.

Change from baseline in Worst Fatigue NRS 
through Week 156.

Change from baseline in Patient Global Impression 
of Severity through Week 156. 

Change from baseline in mental component score 
(MCS), physical component score (PCS), and 
domain scores in the Short-Form 36-item health 
survey version 2 (SF- 36v2) acute through Week 
156.

Change from baseline in FACIT-F total score
through Week 156.

Change from baseline in the EQ-5D-5L through 
Week 156.

Change from baseline in the WPAI-Lupus through 
Week 156.
Abbreviations: CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; EQ-5D-5L = 5-level 
EuroQol-5 Dimensions; FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; 
LLDAS = Lupus Low Disease Activity State; NRS = Numeric Rating Scale; QD = once daily; SLE = systemic 
lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC/ACR
= Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology; 
SRI-4 = Systemic Lupus Erythematosus Responder Index-4; WPAI = Work Productivity and Activity 
Impairment. 

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5. Study Design
5.1.
Overall Design
Study I4V-MC-JAIM [JAIM] is a Phase 3, multicenter, randomized, outpatient, long term
extension trial to evaluate the long-term safety and efficacy of baricitinib in eligible patients with 
SLE who have completed the treatment period in an originating study (such as, 
Study I4V-MC-JAHZ [JAHZ] or Study I4V-MC-JAIA [JAIA]).
Figure JAIM.1 illustrates the study design.
The study consists of 3 periods:
Screening Period:  Screening for JAIM (Week 0, Visit 1) should occur during the last visit of 
the originating study.  However, in particular circumstances, this duration may be extended after 
consultation with the sponsor.
Treatment Period:  Patients randomized to active treatment, baricitinib 4-mg daily or baricitinib 
2-mg daily, during the originating studies will continue on the same, blinded dose of baricitinib 
in Study JAIM.  Patients randomized to placebo during the originating studies will be 
randomized 1:1 to receive blinded baricitinib 2-mg or 4-mg daily during Study JAIM.  
Randomization will be stratified by corticosteroid dose on the day of randomization 
(<10 mg/day; ≥10 mg/day of prednisone or equivalent), and region (defined in the statistical 
analysis plan [SAP]).  Patients originally randomized to active treatment in originating study 
with renal impairment at baseline of the originating study will not receive doses higher than 
2-mg baricitinib QD.  Patients randomized to placebo in the originating study with renal 
impairment (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) at the 
time of randomization to JAIM (assessed by the most recent eGFR from the originating study) 
will receive 2-mg baricitinib QD.  The treatment period will last up to 156 weeks from 
enrollment into Study JAIM.
Patients may continue to receive the background standard therapies for SLE, including a 
corticosteroid, a single antimalarial, and/or a single immunosuppressant, that they were receiving 
at completion of the originating study.
Throughout the trial, investigators should continue to assess individual benefit-risk for patients to 
remain in the trial and should consider discontinuing patients if sufficient clinical benefit is not 
observed with protocol-permitted treatments.
Follow-Up Period:  Patients who complete the treatment period, as well as those who 
discontinue JAIM study treatment early, will have a post-treatment follow-up visit (Visit 801) 
approximately 4 weeks after the last dose of investigational product.

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Abbreviations:  QD = once daily; V visit
a.
Visit 1 of Study JAIM should be completed on the same calendar day as the 
Week-52 visit of the originating study.
b.
The follow-up visit should occur 4 weeks (±5 days) after the last dose of study 
drug.
Figure JAIM.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIM.
5.2.
Number of Participants
Approximately 1100 participants will be enrolled.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Justification for Dose
The 4-mg and 2-mg QD doses of baricitinib selected for this study are based on the Phase 2 SLE 
study, Study JAHH, and are additionally supported by pharmacokinetic (PK), safety, and 
efficacy data for baricitinib in Phase 2 and Phase 3 RA studies and the Phase 2 psoriasis study.  
If, after final analysis of the SLE Phase 3 originating studies, it is determined that either dose of 
baricitinib does not have a positive benefit/risk profile, then that dose arm may be discontinued 
and all patients transferred to the remaining dose arm.

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In the Phase 2 SLE study, baricitinib 4-mg QD demonstrated statistically significant efficacy 
compared to placebo across several relevant measures, including remission of arthritis and/or 
rash (SLEDAI-2K), SRI-4, flare, and LLDAS.  Baricitinib 2-mg QD was numerically better than 
placebo across these measures, although the results were not statistically significant.  Dose 
response patterns favoring baricitinib 4-mg were evident across measures, and improvement was 
observed for both doses in patient-reported outcomes, including worst pain and worst joint pain.  
Pharmacokinetic/pharmacodynamic (PK/PD) modeling suggests the maximum response after 
dosing with 2-mg was not attained by 24 weeks.  Therefore, there is potential that baricitinib 
2-mg will also demonstrate efficacy at Week 52.  No notable safety findings emerged compared 
to the results from baricitinib studies for other indications.
In Phases 2 and 3 RA studies, baricitinib 4-mg QD has demonstrated consistent efficacy; 
baricitinib 2-mg QD was also effective, but was less consistent than 4-mg QD across measures of 
efficacy and patient populations.  Both doses were acceptably safe and well tolerated in the 
context of the efficacy observed and the benefit/risk profiles of other disease-modifying 
antirheumatic drugs.  There was no substantial increase in efficacy noted with doses higher than 
4-mg, where studied.
In the Phase 2 psoriasis study, baricitinib doses between 4-mg and 10-mg were associated with 
statistically significant reductions in measures of disease activity, with greater efficacy at the 
higher doses.  The 2-mg dose did show numeric improvements in efficacy compared with 
placebo.  The 8-mg and 10-mg doses were associated with a higher frequency of AEs related to 
laboratory abnormalities (decreases in hemoglobin, neutrophils, and lymphocytes), while the 
2-mg and 4-mg dose groups had a pattern of AEs similar to placebo.
Dose Adjustment for Renal Impairment
As detailed in the IB, baricitinib exposure increases with decreased renal function (Study 
I4V-MC-JADL).  Based on PK simulations, dose adjustment is not required for patients with 
eGFR ≥60 mL/min/1.73 m2.  Patients with eGFR <60 mL/min/1.73 m2 at screening, who are 
randomized to the 4-mg dose will receive a dose of 2-mg QD, which will ensure that exposures 
do not exceed those of the 4-mg QD dose in patients with eGFR ≥60 mL/min/1.73 m2.  For 
patients randomized to the 2-mg dose, there will be no dose reduction based on renal function.  
See Section 7.2.2 for method of treatment assignment in patients with renal impairment. 

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6.
Study Population
Prospective approval of protocol deviations to enrollment criteria, also known as protocol 
waivers or exemptions, are not permitted.
The study population will be comprised of patients diagnosed with SLE who have completed the 
treatment period of an originating study such as Study JAHZ or Study JAIA. Study investigators 
will review patient records to determine if the patient meets all inclusion and none of the 
exclusion criteria to qualify for participation in the study. 
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria at 
screening:
Type of Patient and Disease Characteristics
[1]
Have completed the final treatment study visit of an originating study, such as 
Study JAHZ or Study JAIA.
Patient Characteristics
[2]
Male or nonpregnant, nonbreastfeeding female patient
a.
Patients of child-bearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex relationship 
(as part of their preferred and usual lifestyle) must agree to either remain 
abstinent or stay in a same-sex relationship without sexual relationships with 
the opposite sex.
b. Total abstinence is defined as refraining from intercourse during the entirety 
of the study and for at least 1 week following the last dose of investigational 
product.  Periodic abstinence, such as calendar, ovulation, symptothermal, 
post-ovulation methods, and withdrawal, are not acceptable methods of 
contraception.
c.
Otherwise, patients of childbearing potential together with their partners must 
agree to use 2 effective methods of contraception, where at least 1 form is 
highly effective, for the entirety of the study and for at least 1 week following 
the last dose of investigational product.
d. The following contraception methods are considered acceptable (the patient 
should choose 2, and 1 must be highly effective [defined as less than 1% 
failure rate per year when used consistently and correctly]):

Highly effective birth control methods:

Combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:  oral, 
intravaginal, or transdermal

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
Progestogen-only containing hormonal contraception associated 
with inhibition of ovulation:  oral, injectable, or implantable

Intrauterine device (IUD)/intrauterine hormone-releasing system 
(IUS)

Vasectomized male (with appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate).

Effective birth control methods:

Male or female condom with spermicide.  It should be noted that 
the use of male and female condoms as a double barrier method is 
not considered acceptable due to the high failure rate when these 
methods are combined.

Diaphragm with spermicide

Cervical sponge

Cervical cap with spermicide
Note:  When local guidelines concerning highly effective or effective 
methods of birth control differ from the above, the local guidelines must 
be followed.
Patients of non‒child-bearing potential are not required to use birth control and 
they are defined as:

Women who are infertile due to surgical sterilization (hysterectomy, 
bilateral oophorectomy, or tubal ligation) 

Post-menopausal – defined either as 

A woman at least 50 years of age with an intact uterus, not on 
hormone therapy, who has had either

Cessation of menses for at least 1 year

At least 6 months of spontaneous amenorrhea with follicle-
stimulating hormone >40 mIU/mL

Women aged 55 years or older who are not on hormone therapy, 
and who have had at least 6 months of spontaneous amenorrhea

Women aged 55 years or older who have a diagnosis of menopause
Informed Consent
[3]
Must read and understand the informed consent approved by Eli Lilly and 
Company (Lilly), or its designee, and the institutional review board (IRB)/ethics 
review board (ERB) governing the site, and provide written informed consent.

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6.2.
Exclusion Criteria
Medical Conditions
[4]
Have significant uncontrolled cerebro-cardiovascular (for example, myocardial 
infarction, unstable angina, unstable arterial hypertension, severe heart failure, or 
cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, endocrine, 
hematologic, neuropsychiatric disorders, or abnormal laboratory values that, in 
the opinion of the investigator, pose an unacceptable risk to the patient if 
investigational product continues to be administered.
[5]
Have a known hypersensitivity to baricitinib or any component of this 
investigational product.
[6]
Had investigational product permanently discontinued at any time during a 
previous baricitinib study.
[7]
Had temporary investigational product interruption at the final study visit of a 
previous baricitinib study and, in the opinion of the investigator, this poses an 
unacceptable risk for the patient’s participation in the study.
[8]
Have any other condition that, in the opinion of the investigator, renders the 
patient unable to understand the nature, scope, and possible consequences of the 
study or precludes the patient from following and completing the protocol.
[9]
Are currently enrolled in any other clinical study involving an investigational 
product or any other type of medical research, judged not to be scientifically or 
medically compatible with this study.
6.3.
Lifestyle Restrictions
Study participants should be instructed not to donate blood or blood products during the study or
for 30 days following the last dose of investigational product.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened.

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7. Treatments
7.1.
Treatments Administered
This study involves baricitinib tablets 4-mg or 2-mg administered orally QD with placebo tablets 
administered orally QD to maintain the blind.  Table JAIM.3 shows the treatment regimens.
Table JAIM.3.
Treatment Regimens
Treatment Group
Treatments Administered Day 1 through Day 1092
Baricitinib 4-mg QDa
1 baricitinib 4-mg tablet and 1 placebo tablet matching baricitinib 2-mg
Baricitinib 2-mg QD
1 baricitinib 2-mg tablet and 1 placebo tablet matching baricitinib 4-mg
Abbreviations:  eGFR = estimated glomerular filtration rate; QD=once daily.
a
Patients randomized to placebo during the originating study with eGFR <60 mL/min/1.73 m2 (based on the last 
eGFR assessment prior to entry into Study JAIM) who are randomized to the 4-mg dose will receive a dose of 
2-mg QD.  Patients randomized to active treatment during the originator study who were receiving an adjusted 
dose due to renal impairment will continue on the same adjusted dose in Study JAIM.
Note:  Patients randomized to placebo during the originating study will be randomized 1:1 to blinded baricitinib 2-
mg or baricitinib 4-mg.  Dose adjustment for patients newly randomized to baricitinib, if necessary, will be based 
on the last available estimated glomerular filtration rate (eGFR) from the originating study.
The investigator or his/her designee is responsible for the following:

Explaining the correct use of the investigational agent(s) to the patient

Verifying that instructions are followed properly

Maintaining accurate records of investigational product dispensing and collection

At the end of the study returning all unused medication to Lilly, or its designee,
unless the sponsor and sites have agreed that all unused medication is to be 
destroyed by the site, as allowed by local law.
7.1.1. Packaging and Labelling
Lilly (or designee) will provide the following primary study materials:

Tablets containing 4-mg of baricitinib

Tablets containing 2-mg of baricitinib

Tablets containing placebo to match 4-mg baricitinib

Tablets containing placebo to match 2-mg baricitinib
Investigational product will be dispensed to the patient at the principal investigator’s study site.  
Investigational product packaging will contain enough tablets for the longest possible interval
between visits.
Investigational product will be labeled according to the country’s regulatory requirements.

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Patients will be instructed to take 2 tablets, 1 tablet from 2 different bottles, each day.
All investigational products will be stored, inventoried, reconciled, and destroyed according to
applicable regulations. Investigational products will be supplied by Lilly or its representative in
accordance with current Good Manufacturing Practices and will be supplied with lot numbers,
expiry dates, and certificates of analysis (as applicable).
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be assigned to baricitinib treatment (2-mg QD 
or 4-mg QD) according to the treatment they were receiving in the originating study.  Patients 
randomized to active treatment during the originating study will be assigned to the same, blinded 
dose of baricitinib in Study JAIM. Patients randomized to placebo during the originating study 
will be randomized 1:1 to blinded baricitinib treatment (2-mg QD or 4-mg QD).  Randomization 
will be stratified by corticosteroid dose on the day of randomization (<10 mg/day; ≥10 mg/day 
prednisone or equivalent), and region (defined in the SAP).  Patients with renal impairment (as 
defined in Section 7.2.2) who are randomized to baricitinib 4-mg QD will receive baricitinib 
2-mg QD.
Assignment to treatment groups will be determined using an interactive web-response system 
(IWRS).  The IWRS will be used to assign packages containing blinded investigational product 
to each patient. Site personnel will confirm that they have located the correct packages by 
entering a confirmation number found on the packages into the IWRS before dispensing to the 
patient.
7.2.1. Selection and Timing of Doses
Investigational product will be provided to patients at Visit 1.
Two tablets should be taken orally each day, without regard to food and, if possible, at 
approximately the same time every day.
7.2.2. Dose Adjustment for Renal Impairment
The dose adjustment for renal impairment will be managed by IWRS to ensure maintenance of 
the treatment blind.  For patients randomized to active treatment during the originating studies, 
the eGFR value from the originating screening visit will be used by IWRS to assign the treatment 
doses accordingly.  For patients randomized to placebo in the originating studies, the last 
available eGFR value from the originating study will used by IWRS to assign the treatment 
doses accordingly.

Patients with documented renal impairment (defined as eGFR ≥40 to 
<60 mL/min/1.73 m2), who are assigned to active treatment (either to the baricitinib 4-mg 
arm or the baricitinib 2-mg arm) will receive a baricitinib 2-mg QD dose by the IWRS.

No dose adjustment will be made for patients with eGFR ≥60 mL/min/1.73 m2.
The rationale of dose adjustment for patients with documented renal impairment is detailed in 
Section 5.4. 

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Interruption criteria due to eGFR during the treatment period is discussed in Section 8.1.1.
7.3.
Blinding
This is a double-blind study.  After database lock of trials JAHZ and JAIA, site personnel and 
patients will remain blinded to treatment assignment.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted.  Patient safety must always be the first 
consideration in making such a determination.  If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the sponsor-designated medical 
monitor prior to unblinding a patient’s treatment assignment, unless this could delay emergency 
treatment of the patient.  If a patient’s treatment assignment is unblinded, Lilly must be notified 
immediately.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment.  All 
calls resulting in an unblinding event are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or patient is unblinded, the patient 
must be discontinued from the study.  In cases where there are ethical reasons to have the patient 
remain in the study, the investigator must obtain specific approval from a Lilly-designated 
medical monitor for the patient to continue in the study.
7.4.
Dosage Modification
During this study, treatment assignment and dose adjustment of investigational product will be 
followed strictly as indicated in Section 7.2.1 and Section 7.2.2.
If, after final analysis of the SLE Phase 3 originating studies, it is determined that either dose of 
baricitinib does not have a positive benefit/risk profile, then that dose arm may be discontinued 
and all patients transferred to the remaining dose arm.  This modification would be made via an 
amendment to this protocol.
See Section 7.7 for permitted concomitant therapy.  
7.5.
Preparation/Handling/Storage/Accountability
All investigational product (used and partially used) will be returned to the sponsor or destroyed
at the site with the sponsor’s written approval. In some cases, sites may destroy the material if,
during the investigative site selection, the evaluator has verified and documented that the site has
appropriate facilities and written procedures to dispose of clinical trial materials.
Storage and handling instructions are provided on the investigational product packaging and 
should be followed.

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7.6.
Treatment Compliance
Patient compliance with investigational product will be assessed at each visit and at Early 
Termination during the treatment period by counting returned tablets. Deviations from the 
prescribed dosage regimen should be recorded in the electronic case report form (eCRF). 
A patient will be considered significantly noncompliant if he or she misses >20% of the 
prescribed doses during the treatment period, unless the patient’s investigational product was 
withheld by the investigator for safety reasons. 
Similarly, a patient will be considered significantly noncompliant if he or she is judged by the 
investigator to have intentionally or repeatedly taken more than the prescribed amount of 
investigational product. Patients found to be noncompliant with the investigational product 
should be assessed to determine the reason for noncompliance and educated and/or managed as 
deemed appropriate by the investigator to improve compliance.
7.7.
Concomitant Therapy
Patients may continue to receive the background standard therapies for SLE they were receiving 
at completion of the originating study.  Changes in dose of background standard therapies for 
SLE, such as an increase in dose of antimalarials or immunosuppressants, are permitted during 
the study.  Initiation of new antimalarials or immunosuppressants are prohibited during the 
study.
In addition, changes in concomitant medication, such as an increase in corticosteroids to manage 
any increase in disease activity or corticosteroid tapering, are permitted during the study in 
accordance with long term management of disease activity and at the investigator’s discretion.  
Any required corticosteroid bursts should be aligned with clinical practice.
Prohibited concomitant treatments include those outlined in the exclusion criteria of the 
originating trials.

Scheduled parenteral corticosteroids, biologic treatments for immunologic disease, 
cyclophosphamide, belimumab, anifrolumab (or any other anti-IFN therapy), rituximab, 
any other B cell depleting therapies, intravenous immunoglobulin or any other JAK 
inhibitors.
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. 
Any additional medication, whether prescription or over-the-counter, used at baseline and/or 
during the course of the study must be documented in the eCRF with start and stop dates.

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7.8.
Treatment after the End of the Study
7.8.1. Treatment after Study Completion
Baricitinib will be made available to patients until the conclusion of the study.  Patients will be
referred to their local treatment centers for continued therapy as clinically indicated.

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Temporary Interruption of Investigational Product
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or abnormal laboratory values that may have an unclear relationship to investigational product.  
It is recommended that the investigator consult with Lilly (or its designee) before temporarily 
interrupting therapy for reasons other than those defined in Table JAIM.4.  Retest timing and 
frequency is at the investigator’s discretion.
Investigational product that was temporarily interrupted because of an AE or abnormal 
laboratory value, not specifically covered in Table JAIM.4, may be restarted at the discretion of 
the investigator.  Investigational product must be held in the following situations and may only 
be resumed as noted in the table.
Table JAIM.4.
Criteria for Temporary Interruption of Investigational Product
Hold Investigational Product if the Following 
Abnormalities Occur:
Investigational Product May be Resumed When:
WBC count <2000 cells/µL
(<2.00 x 103/µL or <2.00 GI/L)
WBC count 2500 cells/µL
(≥2.50 x 103/µL or ≥2.50 GI/L)
ANC <1000 cells/L 
(<1.00 x 103/µL or <1.00 GI/L)
ANC ≥1200 cells/µL
(≥1.2 x 103/µL or ≥1.2 GI/L)
Lymphocyte count <300 cells/µL
(<0.30 x 103/µL or <0.30 GI/L)
Lymphocyte count 500 cells/µL
(≥0.50 x 103/µL or ≥0.50 GI/L)
Platelet count <25,000/µL
(<25 x 103/µL or <25 GI/L)
Platelet count 50,000/µL
(≥50 x 103/µL or ≥50 GI/L)
eGFR <40 mL/min/1.73 m2 for patients with eGFR 
≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
ALT or AST >5 x ULN
ALT and AST return to <2 x ULN and possible DILI has 
been ruled out, and IP is not considered to be the cause of 
enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 9 g/dL (≥90.0 g/L)
Symptomatic herpes zoster
All skin lesions have crusted and are resolving
Infection that, in the opinion of the investigator, 
merits the IP being withhelda
Resolution of infection that, in the opinion of the 
investigator, merits the IP being restarted
Abbreviations:  ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; WBC = white blood cell.
a
Permanent discontinuation of IP should be considered for patients who develop a serious infection that, in the 
opinion of the investigator, would pose an unacceptable risk if IP were resumed.

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8.1.2. Permanent Discontinuation from Study Treatment
Possible reasons leading to permanent discontinuation of investigational product:

Subject Decision
o
The patient requests to discontinue investigational product.

Investigator Decision
o
The investigator decides that the patient should be discontinued from investigational 
product.

Discontinuation due to a hepatic event or liver test abnormality.  Patients who are 
discontinued from investigational product due to a hepatic event or liver test abnormality 
should have additional hepatic safety data collected via eCRF.
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:
o
ALT or AST >8 x upper limit of normal (ULN)
o
ALT or AST >5 x ULN for more than 2 weeks after temporary interruption of 
investigational product
o
ALT or AST >3 x ULN and either total bilirubin level (TBL) >2 x ULN or 
international normalized ratio >1.5 
o
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%)
o
Alkaline phosphatase (ALP) >3 x ULN
o
ALP >2.5 x ULN and TBL >2 x ULN
o
ALP >2.5 x ULN, with the appearance of fatigue, nausea, vomiting, right quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%)

Discontinuation due to Other Laboratory Abnormalities:
o
White blood cell count <1000 cells/µL (1.00x103/µL or 1.00 GI/L)
o
Absolute neutrophil count <500 cells/µL (0.50x103/µL or 0.50 GI/L)
o
Lymphocyte count <200 cells/µL (0.20x103/µL or 0.20 GI/L)
o
Hemoglobin <6.5 g/dL (<65.0 g/L)
Temporary interruption rules (see Section 8.1.1) must be followed where applicable.  For lab 
values that meet permanent discontinuation thresholds, investigational product should be 
discontinued.  However, if in the opinion of the investigator, the lab abnormality is due to 
intercurrent illness or another identified factor, lab tests may be repeated. The investigator may 
be able to restart investigational product after consultation with the Lilly-designated medical 

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monitor, only when the lab value meets resumption thresholds (Table JAIM.4) following the 
resolution of the intercurrent illness or other identified factor.

Discontinuations due to other circumstances:
o
Pregnancy
o
Malignancy (except for successfully treated basal cell or squamous epithelial skin 
cancers)
o
Hepatitis B virus DNA is detected with a value above the lower limit of quantitation
(see Section 9.4.6). 
o
Occurrence of a VTE (DVT/pulmonary embolism [PE]) during the study
o
Serious infection, that in the opinion of the investigator merits the investigational 
product being discontinued
o
If the patient, for any reason, requires treatment with another therapeutic agent that 
may be effective for treatment of SLE that is noncompliant to the concomitant 
therapy requirements (see Section 7.7) during the study.  Discontinuation from the 
investigational product must occur prior to introduction of the new agent.
Throughout the trial, investigators should continue to assess benefit-risk for patients to remain in
the trial, and should consider discontinuing patients if sufficient clinical benefit is not observed
with protocol allowed treatments.
Patients discontinuing from study treatment prematurely for any reason, should complete AE and 
other safety follow-up per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol and proceed to the post-treatment follow up period.
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study treatment, unless there 
are extenuating circumstances that make it medically necessary for the patient to continue on 
study treatment.  If the investigator and the sponsor-designated medical monitor agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
sponsor-designated medical monitor to allow the inadvertently enrolled patient to continue in the 
study with or without treatment with investigational product. Safety follow up is as outlined in 
Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of this
protocol.
8.2.
Discontinuation from the Study
Patients will be discontinued in the following circumstances:

Enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study

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
Participation in the study needs to be stopped for medical, safety, regulatory, 
or other reasons consistent with applicable laws, regulations, and good clinical 
practice 

Investigator decision
o
The investigator decides that the patient should be discontinued from the 
study

Subject decision
o
The patient requests to be withdrawn from the study
Patients discontinuing from the study prematurely for any reason, should complete AE and other 
safety follow-up as indicated in the Early Termination Visit per Section 2 (Schedule of 
Activities), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of this protocol and proceed 
to the post-treatment follow up period.
8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.

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9.
Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Secondary Efficacy Assessments
9.1.1.1.
Systemic Lupus Responder Index
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 
British Isles Lupus Assessment Group (BILAG) and Physician’s Global Assessment of Disease 
Activity components ensure that the improvement in overall disease is not accompanied by 
disease worsening in other organ systems.  The SRI-4 response is defined as follows:

Reduction of ≥4 points from baseline in SLEDAI-2K score (Section 9.1.1.2); and

No new BILAG A or no more than 1 new BILAG B disease activity scores
(Section 9.1.1.3); and

No worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in 
Physician’s Global Assessment of Disease Activity (Section 9.1.1.4).
9.1.1.2.
Systemic Lupus Erythematosus Disease Activity Index-2000
The SLEDAI-2K is a validated global disease activity instrument that focuses on high-impact 
disease manifestations across 9 organ systems.  It includes 24 clinical and laboratory variables 
with manifestations graded by the affected organ system.  CNS:  Seizure, Psychosis, Organic 
Brain Syndrome, Visual Disturbance, Cranial Nerve Disorder, Lupus Headache, Cerebrovascular 
attack; Vascular:  Vasculitis; Musculoskeletal:  Arthritis, Myositis; Renal:  Urinary Casts, 
Hematuria, Proteinuria, Pyuria; Mucocutaneous:  Rash, Alopecia, Mucosal Ulcers; 
Cardiovascular and Respiratory:  Pleurisy, Pericarditis; Immunologic:  Low complement, 
Increased DNA Binding; Constitutional:  Fever; Hematologic:  Thrombocytopenia, Leukopenia.
9.1.1.3.
British Isles Lupus Assessment Group 2004 Index
The BILAG-2004 Index is a validated global disease activity index designed on the basis of the 
physician’s intention to treat, 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, 

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cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematology.  A BILAG A disease 
activity score is severe disease activity requiring high-dose oral or intravenous corticosteroids, 
immunomodulators, or high-dose anticoagulation along with high-dose corticosteroids or 
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 that the system was never involved.
9.1.1.4.
Physician’s Global Assessment of Disease Activity
The Physician’s Global Assessment of Disease Activity is the physician’s assessment of the 
patient’s overall disease activity due to SLE, as compared with all possible patients with SLE. 
The Physician’s Global Assessment of Disease Activity is scored using a 100-mm Visual Analog 
Scale (VAS), where 0 mm (measured from the left starting point of the line) indicates no disease 
activity and 100 mm (measured from the left starting point of the line) indicates the most severe 
disease activity possible for all patients with SLE (or death). The Physician’s Global 
Assessment of Disease Activity score is indicated by making a vertical tick mark on the line 
between 0 and 100 mm. There are benchmarks of 0 (0 mm), 1 (33 mm), 2 (67 mm), and 3 
(100 mm) on the line corresponding to no, mild, moderate, and severe SLE disease activity, 
respectively.
9.1.1.5.
Systemic Lupus Erythematosus Responder Index
The SRI-5, -6, -7, and -8 will also be assessed, and are similar to the SRI-4, except that they 
require a reduction of ≥5, 6, 7, or 8 points (respectively) from baseline in SLEDAI-2K score. 
For assessment description, see Section 9.1.1.1.
9.1.1.6.
Safety of Estrogens in Lupus Erythematosus National Assessment 
(SELENA)-Systemic Lupus Erythematosus Disease Activity Index 
(SLEDAI) Flare Index
The SELENA-SLEDAI Flare Index (SFI) uses the SLEDAI score, disease activity scenarios, 
treatment changes, and Physician’s Global Assessment of Disease Activity to define 
mild/moderate and severe flares.  The index takes into account the absolute change in total 
scores, new or worsening symptoms, and increases in medication use or hospitalization due to 
the disease activity.
9.1.1.7.
Cutaneous Lupus Erythematosus Disease Area and Severity Index
The Cutaneous Lupus Erythematosus Disease Area and Severity Index is a validated scale used 
to assess cutaneous manifestations of SLE consisting of 2 scores. The first summarizes the 
activity of the disease, while the second is a measure of the damage done by the disease.  
Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane 
involvement, acute hair loss, and nonscarring alopecia. Damage is scored in terms of 
dyspigmentation and scarring, including scarring alopecia.
9.1.1.8.
Lupus Low Disease Activity State
The LLDAS is defined as a low level of disease activity attained with or without use of low-dose 
steroids and/or tolerated standard maintenance doses of SoC medications.

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9.1.1.9.
Tender/Swollen Joint Count (28 Joints)
The 28 joints to be examined and assessed as tender or not tender for tender joint count and as 
swollen or not swollen for swollen joint count include 14 joints on each side of the patient’s 
body:  the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 
interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees.
9.1.1.10. Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology Damage Index
The SLICC/ACR Damage Index is scored on 41 items representing damage to 12 organ systems.  
The index records damage occurring in patients with SLE regardless of its cause and includes 
specific comorbidities associated with SLE that may be due to treatment-related toxicity.
9.1.1.11. Health Outcomes and Quality of Life Measures
The self-reported questionnaires will be administered via an on-site electronic clinical outcome 
assessment device as specified in the Schedule of Activities (Section 2) in countries where the 
questionnaires have been translated into the native language of the region and linguistically 
validated.
9.1.1.11.1.Worst Pain Numeric Rating Scale 
The Worst Pain numerical rating scale (NRS) is a single-item, patient-administered, 11-point 
horizontal scale anchored at 0 and 10, with 0 representing “no pain” and 10 representing “pain as 
bad as you can imagine.” Overall severity of a patient’s pain is indicated by selecting the 
number that best describes the worst level of pain during the past 7 days. Data will be captured 
on an electronic tablet collected at site visits.
9.1.1.11.2.Worst Joint Pain Numeric Rating Scale
The Worst Joint Pain NRS is a single-item, patient-administered, 11-point horizontal scale 
anchored at 0 and 10, with 0 representing “no joint pain” and 10 representing “joint pain as bad 
as you can imagine.” Overall severity of a patient’s joint pain is indicated by selecting the 
number that best describes the worst level of joint pain during the past 7 days.  Data will be 
captured on an electronic tablet collected at site visits.
9.1.1.11.3.Worst Fatigue Numeric Rating Scale
The Worst Fatigue NRS is a single-item, patient-administered, 11-point horizontal scale 
anchored at 0 and 10, with 0 representing “no fatigue” and 10 representing “as bad as you can 
imagine.” Overall severity of a patient’s fatigue is indicated by selecting the number that best 
describes the worst level of fatigue during the past 7 days.  Data will be captured on an electronic 
tablet collected at site visits.
9.1.1.11.4.Patient’s Global Impression of Severity
The Patient’s Global Impression of Severity is a single-item question asking the patient how they 
would rate their overall lupus symptoms over the past 7 days.  The 5 categories of response range 
from “no symptoms” to “severe”.  Data will be captured on an electronic tablet collected at site 
visits.

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9.1.1.11.5.Medical Outcomes Short-Form 36-Item Health Survey Version 2 
(SF-36v2)
The Short-Form 36-item Health Survey version 2 (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 physical component score and the 
mental component score, will be evaluated based on the 8 SF-36v2 Acute domains. The acute 
version of this instrument has a 1 week recall period (Brazier et al. 1992; Ware and Sherbourne 
1992). Data will be captured on an electronic tablet collected at site visits.
9.1.1.11.6.Functional Assessment of Chronic Illness Therapy–Fatigue Scale
The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (Cella and 
Webster 1997) is a brief, 13-item, symptom-specific questionnaire that specifically assesses the 
self-reported severity of fatigue and its impact upon daily activities and functioning. The 
FACIT-Fatigue uses 0 (“not at all”) to 4 (“very much”) NRS to assess fatigue and its impact in 
the past 7 days. Scores range from 0 to 52, with higher scores indicating less fatigue. Data will 
be captured on an electronic tablet collected at site visits.
9.1.1.11.7.Work Productivity and Activity Impairment Questionnaire–Lupus
The Work Productivity and Activity Impairment Questionnaire-Lupus (WPAI-Lupus) records 
impairment due to Lupus during the past 7 days.  The WPAI-Lupus consists of 6 items grouped 
into 4 domains:  absenteeism (work time missed), presenteeism (impairment at work/reduced 
on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus 
presenteeism), and activity impairment.  Scores are calculated as impairment percentages (Reilly 
et al. 1993), with higher scores indicating greater impairment and less productivity.  Data will be 
captured on an electronic tablet collected at site visits.
9.1.1.11.8.European Quality of Life-5 Dimensions-5 Levels
The European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) is a standardized measure of 
health status in order to provide a simple, generic measure of health for clinical and economic 
appraisal.  The EQ-5D-5L consists of 2 components:  a descriptive system of the respondent’s 
health and a rating of his/her current health state using a 0- to 100-mm VAS.  The descriptive 
system comprises the following 5 dimensions:  mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression.  Each dimension has 5 levels:  no problems, slight 
problems, moderate problems, severe problems, and extreme problems.  The respondent is asked 
to indicate his or her health state by ticking (or placing a cross) in the box associated with the 
most appropriate statement in each of the 5 dimensions.  It should be noted that the numerals 1 to 
5 have no arithmetic properties and should not be used as an ordinal score.  The VAS records the 
respondent’s self-rated health on a vertical VAS where the endpoints are labeled “best 
imaginable health state” and “worst imaginable health state.”  This information can be used as a 
quantitative measure of health outcome.  The EQ-5D-5L health states, defined by the EQ-5D-5L 
descriptive system, may be converted into a single summary index by applying a formula that 

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

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9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

Death

Initial or prolonged inpatient hospitalization

A life-threatening experience (that is, immediate risk of dying)

Persistent or significant disability/incapacity

Congenital anomaly/birth defect

Important medical events that may not be immediately life-threatening or result in 
death or hospitalization, but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above.
All AEs occurring after signing the ICF are recorded in the eCRF and assessed for serious 
criteria.  The SAE reporting to the sponsor begins after the patient has signed the ICF and has 
received investigational product.  However, if an SAE occurs after signing the ICF, but prior to 
receiving investigational product, the SAE should be reported to the sponsor according to
SAE-reporting requirements and timelines, if it is considered reasonably possibly related to study 
procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a paper SAE form.  If alerts are issued via telephone, they are to be 
immediately followed with official notification on study-specific SAE forms.  The SAE form 
should be completed by the investigator, and submitted via fax to the sponsor’s global patient 
safety department.  This form includes a fax cover page that is pre-populated with the 
appropriate fax number.  The 24-hour notification requirement refers to the initial SAE 
information and all follow-up SAE information.  Patients with a serious hepatic AE should have 
additional data collected using the eCRF.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient disposition CRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he or she considers the event reasonably possibly related to 
the study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidances or national regulatory requirements in participating countries 
require the reporting of SUSARs.  Lilly has procedures that will be followed for the 

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identification, recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances.
9.2.2. Adverse Events of Special Interest
Adverse events of special interest (AESIs) will include the following: 

Infections (including TB, herpes zoster, or opportunistic infections)

Malignancies

Hepatic events (see Section 9.4.7)

MACE (see Section 9.4.8)

VTE (DVT/PE) (see Section 9.4.9). 
Sites will provide details on these AEs as instructed on the eCRF and may be asked for 
additional description by Lilly.
9.2.3. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
Refer to the IB.
9.4.
Safety
Any clinically significant findings from physical examination, vital signs measurements, or 
laboratory measurements that result in a diagnosis and that occur after the patient receives the 
first dose of study treatment should be reported to Lilly or its designee as an AE via eCRF.
9.4.1. Vital Signs
For each patient, vital signs measurements (sitting blood pressure, heart rate, and temperature) 
should be conducted according to the Schedule of Activities (Section 2).  Subjects should be 
seated and relaxed with both feet on the floor for at least 5 minutes prior to taking measurements.  
Three replicate blood pressure readings should be made at each time point at approximately 
30- to 60-second intervals.  A single-pulse measurement should be taken simultaneously with at 
least 1 of the blood pressure readings.  Blood pressure and pulse measurements should be made 
using either automated or manual equipment.  If measurements are machine averaged, the 
average blood pressure reading should be recorded on the CRF.  If measurements are manual or 
the machine does not provide an average reading, then each individual reading should be 
recorded on the CRF.  Measurements should be made before any scheduled blood draws.  
Additional measurements of vital signs may be performed at the discretion of the investigator.

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9.4.2. Physical Examination
For each patient, symptom-directed physical examinations will be conducted according to the 
Schedule of Activities (Section 2).
9.4.3. Laboratory Tests
For each patient, laboratory tests detailed in Appendix 2 should be conducted according to the 
Schedule of Activities (Section 2). 
With the exception of laboratory test results that may unblind the study, Lilly or its designee will 
provide the investigator with the results of laboratory tests analyzed by a central vendor, if a 
central vendor is used for the clinical trial.
9.4.4. Columbia-Suicide Severity Rating Scale
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and 
frequency of suicidal ideation and/or behavior during the assessment period.  The scale includes 
suggested questions to solicit the type of information needed to determine if suicidal ideation 
and/or behavior occurred.  The C-SSRS is administered by an appropriately trained health care 
professional with at least 1 year of patient care/clinical experience.  The tool was developed by 
the National Institute of Mental Health trial group for the purpose of being a counterpart to the 
Columbia Classification Algorithm of Suicide Assessment categorization of suicidal events.  For 
this study, the scale has been adapted (with permission from the scale authors) to include only 
the portion of the scale that captures the occurrence of the 11 preferred ideation and behavior 
categories.
The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the Self-Harm Follow-Up Form.  The 
Self-Harm Follow-Up Form is a series of questions that provides a more detailed description of 
the behavior cases.
9.4.5. 16-Item Quick Inventory of Depressive Symptomatology-Self 
Report
The 16-item Quick Inventory of Depressive Symptomatology-Self Report is a self-administered,
16-item instrument, intended to assess the existence and severity of symptoms of depression as 
listed in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental 
Disorders, 5th Edition (APA 2013).  A patient is asked to consider each statement as it relates to 

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the way they have felt for the past 7 days.  There is a 4-point scale for each item ranging from 0 
to 3.  The 16 items corresponding to 9 depression domains are summed to give a single score 
ranging from 0 to 27, with higher scores denoting greater symptom severity.  The domains 
assessed by the instrument include:  (1) sad mood, (2) concentration, (3) self-criticism, (4) 
suicidal ideation, (5) interest, (6) energy/fatigue, (7) sleep disturbance (initial, middle, and late 
insomnia or hypersomnia), (8) decrease/increase in appetite/weight, and (9) psychomotor 
agitation/retardation.
9.4.6. Hepatitis B Virus (HBV) DNA Monitoring
Patients who were hepatitis B core antibody positive at screening for the originating study will 
continue to require Hepatitis B virus (HBV) DNA monitoring approximately every 3 months up 
to Week 60, thereafter reducing to every 6 months, regardless of their hepatitis B surface 
antibody status.
The following actions should be taken in response to HBV DNA test results:

If a single result is obtained with a value “below limit of quantitation,” the test should be 
repeated within approximately 2 weeks.  

If the repeat test result is “target not detected,” monitoring may resume according to the 
study schedule.

If the patient has 2 or more test results with a value “below limit of quantitation” during 
the study, HBV DNA testing should be performed approximately once per month for the 
remainder of the study and referral to a hepatologist is recommended. 

If a result is obtained with a value above limit of quantitation at any time during the 
study, the patient will be permanently discontinued from investigational product (see 
Section 8.1.1) and should be referred to a hepatology specialist immediately.
o
In selected cases, investigators may temporarily continue investigational product in 
accordance with current immunomodulator management in the setting of HBV DNA 
positivity.  This option may be considered in consultation with Lilly (or its designee) 
and after evaluation of individual patient risks and benefits.
9.4.7. Hepatic Safety Monitoring
If a study patient experiences elevated ALT ≥3 x ULN, ALP ≥2 x ULN, or elevated TBL ≥2 x
ULN, liver testing (Appendix 4) should be repeated within 3 to 5 days, including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor.  Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels. 
Discontinuation criteria of investigational products, either temporary interruption or permanent 
discontinuation, due to abnormal ALT, AST, TBL, or ALP, are detailed in Section 8.1.  

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Hepatic Safety Data Collection
Additional safety data should be collected via the eCRF if 1 or more of the following conditions 
occur: 

Elevation of serum ALT to ≥5 x ULN on 2 or more consecutive blood tests

Elevated serum TBL to ≥ 2 x ULN (except for cases of known Gilbert’s syndrome) 

Elevation of serum ALP to ≥2 x ULN on 2 or more consecutive blood tests

Patient discontinued from treatment due to a hepatic event or abnormality of liver tests

Hepatic event considered to be a SAE
9.4.8. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
The Lilly-designated medical monitor will monitor safety data throughout the course of the 
study.  Lilly will review SAEs within time frames mandated by company procedures.  The Lilly-
designated medical monitor will, as is appropriate, consult with the functionally independent 
Global Patient Safety (GPS) therapeutic area physician or clinical scientist and periodically 
review trends in safety data and laboratory analytes.  Any concerning trends in frequency or 
severity noted by an investigator and/or Lilly or its designee may require further evaluation.
All deaths and SAE reports will be reviewed in a blinded manner by Lilly during the clinical 
trial.  These reports will be reviewed to ensure completeness and accuracy, but will not be 
unblinded to Lilly during the clinical trial.  If a death or clinical AE is deemed serious, 
unexpected, and possibly related to investigational product, 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.
Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular events. Adverse event reports and vital signs will be collected at each study visit. 
The cardiovascular monitoring plan includes the following:

Regular monitoring of lipid levels

Potential MACE (cardiovascular death, myocardial infarction, stroke), other 
cardiovascular events (such as, hospitalization for unstable angina, hospitalization for 
heart failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary 
interventions), venous thrombotic events and noncardiovascular deaths will be identified 
by the investigative site or through medical review and will be sent to a blinded Clinical 
Event Committee for adjudication at regular intervals.
9.4.9. Venous Thromboembolic Events
If a patient develops clinical features of a DVT or PE, appropriate local laboratory tests and 
imaging should be performed, as necessary, for the diagnosis of the event.  For confirmed cases, 

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the patient will be discontinued from study treatment and additional laboratory testing is 
recommended as outlined in Appendix 5.  All suspected VTE events will be independently 
adjudicated by a blinded Clinical Event Committee.
9.5.
Pharmacokinetics
Not Applicable.
9.6.
Pharmacodynamics
Samples collected to measure PD markers, including, but not limited to, anti-dsDNA and 
complement will be identified by the patient number (coded) and retained at a facility selected by 
Lilly or its designee for a maximum of 1 year following last patient visit for the study. 
9.7.
Pharmacogenomics
9.7.1. Whole Blood Samples for Pharmacogenetic Research
Not applicable.
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, PD, mechanism of action, variability of patient response (including safety), and 
clinical outcome.  Sample collection is incorporated into clinical studies to enable examination of 
these questions through measurement of biomolecules, including proteins, lipids, and other 
cellular elements.
Serum, plasma, and urine samples for biomarker research will be collected at the times specified 
in the Schedule of Activities (Section 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, mechanism of action of baricitinib, and/or research 
method or in validating diagnostic tools or assay(s) related to SLE.  
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and ERBs/IRBs 
impose shorter time limits.  This retention period enables use of new technologies, response to 
regulatory questions, and investigation of variable response that may not be observed until later 
in the development of baricitinib or after baricitinib become(s) commercially available.  Any 
samples remaining after 15 years will be destroyed.
9.9.
Medical Resource Utilization and Health Economics
Health Economics and Medical Resource Utilization parameters will not be evaluated in this 
study.

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10. Statistical Considerations
10.1. Sample Size Determination
It is expected that 80% of patients will complete Study JAHZ or JAIA and approximately 90% of 
patients who complete will enter Study JAIM; therefore, planned enrollment into JAIM from 
these originating studies will be approximately 1100 patients.  Additional patients may enroll 
from addenda or other studies.   
10.2. Populations for Analyses
For purposes of analysis of Study JAIM, the following populations are defined:
Population
Description
Modified intent to treat (mITT)
Population
All patients who receive at least 1 dose of investigational product in Study 
JAIM will be included in the mITT population. 
Safety Population
The safety population for JAIM is defined as all patients who receive at least 1 
dose of investigational product in Study JAIM and who did not discontinue from 
the study for the reason ‘Lost to Follow-up’ at the first postbaseline visit. 
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee. A detailed 
SAP describing the statistical methodologies will be developed by Lilly or its designee.
Depending on the efficacy and health outcomes analysis, baseline may be defined as the last 
assessment prior to the first dose of active study drug in Study JAIM or as baseline from the 
originating study.  Depending on the analysis, treatment groups can be based on assignment in 
JAIM, or could be further subdivided based on treatment group assignment in the originating 
studies.
Some of the efficacy and safety endpoints may be better assessed in the context of integrating 
data from the originating studies (and possibly other relevant studies).  The SAP for this study 
and the SAPs which specify integrated analyses, will include details of which analyses will be 
performed on JAIM alone and which will be performed in an integrated fashion (including 
originating studies and possibly other studies).  The exact definition of baseline, populations, and 
treatment groups will depend on the particular analysis (integrated vs. JAIM alone).  
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated. Adjustment for multiple comparisons will not be made.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.

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10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
A detailed description of patient disposition by treatment will be summarized with reasons for 
discontinuation.  Frequency counts and percentages will be presented for each treatment group.  
All patients who discontinue from the study will be identified, and the extent of their 
participation in the study will be reported along with their reason for discontinuation.
10.3.2.2. Patient Characteristics
Demographic and baseline characteristics will be summarized descriptively by treatment group.  
Descriptive statistics, including number of patients, mean, standard deviation, median, minimum, 
and maximum, will be provided for continuous measures, and frequency counts and percentages 
will be tabulated for categorical measures.  No formal statistical comparisons will be made 
among treatment groups unless otherwise stated.  A complete list of patient characteristics and 
baseline clinical measures will be provided in the SAP.
10.3.2.3. Concomitant Therapy
Concomitant medications will be coded and descriptively summarized by treatment group in 
terms of frequencies and percentages using the safety population.
10.3.2.4. Treatment Compliance
Compliance with investigational product treatment will be assessed through counts of returned 
investigational product tablets.  A patient will be considered significantly noncompliant if he or 
she misses more than 20% of the prescribed doses during the study, that is, compliance <80%. 
Similarly, a patient will be considered significantly noncompliant if he or she is judged by the 
investigator to have intentionally or repeatedly taken more than the prescribed amount of 
medication.
10.3.3. Efficacy Analyses
Efficacy and health outcomes analyses will generally be summarized using descriptive statistics.  
The number and percentage of patients maintaining or achieving a categorical efficacy or health 
outcomes response will be summarized. The mean change from baseline of continuous measures 
will be summarized using mixed model repeated measures (MMRM), except for SLICC/ACR 
which will be analyzed using analysis of covariance (ANCOVA).  The MMRM model will 
include treatment, region, visit, treatment-by-visit interaction as fixed categorical effects, and 
baseline value and baseline value-by-visit interaction as fixed continuous effects to estimate 
change from baseline across postbaseline visits. Additional factors, such as originating study 
(JAHZ, JAIA) and originating study stratification factors, may also be included in the model. 
The ANCOVA model for analyzing SLICC/ACR will be based on the same model factors as the 
MMRM analyses, excluding visit and value-by-visit interaction terms. Additional details, 
including any outcomes that will utilize statistical inference and use of originating study data, 
will be provided in the JAIM SAP or the integrated efficacy analysis plan (IEAP), which will 
define how the efficacy and health outcomes data from the Phase 2 and 3 studies will be 
analyzed when combined.

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10.3.3.1. Missing Data Imputation
Missing data will be imputed at specified time points utilizing methodologies, including the 
following:

Modified Last Observation Carried Forward:  The last observed value (non-missing 
value) is used to fill in missing values at a later time point.

Nonresponder imputation: Patients who discontinue treatment early will be defined as 
nonresponders.
The SAP will stipulate which methodology will be utilized for specific analyses.
10.3.4. Safety Analyses
Safety assessments will include AEs, laboratory analytes, vital signs, and questionnaires to 
assess the existence and severity of depression.
The primary endpoints of safety and tolerability will be analyzed as part of the integrated safety 
analyses for SLE.  All details of these integrated analyses will be contained in the integrated 
safety analysis plan for SLE. 
Categorical safety measures for JAIM alone will be summarized with percentages, and incidence 
rates where appropriate.  The following summaries will be reported specifically for JAIM:

patients who permanently discontinue from study drug due to adverse events, 

patients reporting SAEs during the treatment period, 

patients with at least 1 temporary interruption of study drug

patients who permanently discontinued study drug prior to full study completion
Additional details, including any measures that will utilize inferential statistics, will be specified 
in the SAP and/or iSAP.
10.3.4.1. Adverse Events
Adverse events are classified based upon the Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment-emergent adverse events are defined as AEs that first occurred or 
worsened in severity on or after baseline. The number of TEAEs, as well as the number and 
percentage of patients who reported at least 1 TEAE will be summarized using MedDRA for 
each system organ class (or a body system) and each preferred term by treatment group. For 
events that are gender-specific, the denominator and computation of the percentage will only 
include patients from the given gender.
Serious adverse events (including deaths), treatment-emergent AESIs, and AEs that lead to 
investigational product discontinuation will also be summarized using MedDRA for each system 
organ class and each preferred term by treatment group.  Potential AESIs will be identified by a 
standardized MedDRA query or a Lilly-defined MedDRA query.  Details of the AESIs 
(including but not limited to those listed in Section 9.2.2) and analysis will be documented in the 
iSAP.

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10.3.4.2. Clinical Laboratory Tests
All clinical laboratory results will be descriptively summarized by treatment group.  Individual 
results that are outside the normal reference ranges will be flagged in data listings.  Quantitative 
clinical hematology, chemistry, variables obtained at the baseline to postbaseline visits will be 
summarized as changes from baseline.  Categorical variables, including the incidence of 
abnormal values and incidence of AESIs, will be summarized by frequency and percentage of 
patients in corresponding categories. 
10.3.4.3. Vital Signs, Physical Findings, and Other Safety Evaluation
Observed values and changes from baseline (predose or screening if missing) for vital signs and 
physical characteristics, and other continuous safety measures will be descriptively summarized 
by treatment group and time point.  Shift tables will be presented where appropriate.
Summary tables or listings for the C-SSRS and the Self-Harm Supplement Form will be 
produced as needed.
The incidence and average duration of investigational product interruptions will be summarized 
and compared descriptively among treatment groups.  Various techniques may be used to 
estimate the effects of investigational product interruptions on safety measures.  
10.3.5. Subgroup Analyses
Subgroup analyses for selected safety, efficacy or health outcomes parameters may be performed 
if needed.  Details will be provided in the SAP, iSAP or IEAP.
10.3.6. Interim Analyses
A data monitoring committee (DMC) will oversee the conduct of all the Phase 3 clinical trials 
evaluating baricitinib in patients with SLE.  The DMC will consist of members external to Lilly.  
This DMC will follow the rules defined in the DMC charter, focusing on potential and identified 
risks for this molecule and for this class of compounds.  Data monitoring committee membership 
will include, at a minimum, specialists with expertise in rheumatology and statistics.  This DMC 
for studies of patients with SLE may be coordinated with the DMC(s) for other ongoing studies 
of baricitinib in other indications.  Details of the DMC will be documented in a DMC charter.
Periodic data cut offs are planned, and efficacy and safety analyses will be conducted for the 
purpose of regulatory submission or publication. 

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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
ACR
American College of Rheumatology
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
AESI
adverse events of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
anti-dsDNA
anti-double-stranded deoxyribonucleic acid
AST
aspartate aminotransferase
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.
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.
compliance
Adherence to all study-related, good clinical practice, and applicable regulatory 
requirements.
CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
DMC
data monitoring committee
DVT
deep vein thrombosis
eCOA
electronic clinical outcome assessments
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate

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enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the study are 
those who have been assigned to a treatment.
enter
Patients entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives.
EQ-5D-5L
European Quality of Life-5 Dimensions 5 Levels
ERB
ethics review board
FACIT
Functional Assessment of Chronic Illness Therapy
GCP
good clinical practice
GPS
Global Patient Safety
HBV
Hepatitis B virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEAP
integrated efficacy analysis plan
IFN
interferon
IL
interleukin
Informed consent
A process by which a patient voluntarily confirms his or her willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the patient’s decision to participate.  Informed consent is documented by 
means of a written, signed and dated informed consent form.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB
institutional review board
iSAP
integrated SAP
IVRS
interactive voice-response system
IWRS
interactive web-response system
JAK
Janus kinase
LLDAS
lupus low disease activity score
MACE
major adverse cardiovascular events

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MedDRA
Medical Dictionary for Regulatory Activities
MMRM
mixed model repeated measures
NRS
numerical rating scale
NSAID
nonsteroidal anti-inflammatory drug
PD
pharmacodynamics
PE
pulmonary embolism
PK
pharmacokinetics
PRO/ePRO
patient-reported outcomes/electronic patient-reported outcomes
PSAP
program safety analysis plan
QD
once daily
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-36v2
Short-Form 36-item Health Survey version 2
SLE
systemic lupus erythematosus
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SLICC
Systemic Lupus Erythematosus International Collaborating Clinics
SoC
standard of care
SRI-4
Systemic Lupus Erythematosus Responder Index-4
STAT
signal transducers and activators of transcription
SUSARs
suspected unexpected serious adverse reactions
TB
tuberculosis
TBL
total bilirubin level
TEAE
treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
TYK
tyrosine kinase

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ULN
upper limit of normal
VAS
Visual Analog Scale
VTE
venous thromboembolic event
WPAI-Lupus
Work Productivity and Activity Impairment Questionnaire-Lupus

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Appendix 2.
Clinical Laboratory Tests
Clinical Laboratory Testsa
Hematologyb
Clinical Chemistryb
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Absolute reticulocyte count
Total bilirubin
Mean cell volume (MCV)
Direct bilirubin
Mean platelet volume
Alkaline phosphatase (ALP)
Mean cell hemoglobin (MCH)
Alanine aminotransaminase (ALT)/serum glutamic pyruvic 
transaminase
Mean cell hemoglobin concentration 
(MCHC) Leukocytes (WBC)
Aspartate aminotransferase (AST)/serum glutamic 
oxaloacetic transaminase 
Absolute count of 
Neutrophils, segmented
Blood urea nitrogen (BUN)
Neutrophils, juvenile (bands)
Creatinine
Lymphocytes
Estimated glomerular filtration rate (eGFR)c
Monocytes
Uric acid
Eosinophils
Calcium
Basophils
Glucosed
Platelets
Albumin
Cell morphology
Creatine phosphokinase (CPK)
Differential and blood smeare
Total protein
Lipid Profiled,f
Total cholesterol
Urinalysisb
High-density lipoprotein cholesterol (HDL-C)
Color
Low-density lipoprotein cholesterol (LDL-C)
Specific gravity
Triglycerides 
pH
Urine Protein
Glucose
Other Tests
Ketones
Urine pregnancy test (females only)g
Blood
HBV DNAi
Bilirubin
Serum immunoglobulins (IgG, IgA, IgM)
Urobilinogen
Stored serum, plasma, and urine samples for exploratory 
biomarker analyses
Leukocyte esterase
Lupus anticoagulant (dRVVT)
Nitrite
Complement C3 and C4
Microscopic examination of sedimenth
Anti-beta2 glycoprotein-I (IgG, IgM)
Urine creatinine
Urine protein
Urine protein-creatinine ratio

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Autoantibodies
Anti-nuclear antibody (ANA)
Anti-double-stranded DNA (anti-dsDNA) 
antibody
Autoantibodies (anti-RNP, anti-Sm, anti-
SSA/Ro, anti-SSB/La)
Anti-cardiolipin antibodies IgG, IgA, IgM
Abbreviations:  anti-dsDNA = anti-double-stranded deoxyribonucleic acid; dRVVT = Dilute Russell’s Viper Venom 
Time; HBcAb = hepatitis B core antibody; HBV DNA = hepatitis B virus deoxyribonucleic acid; 
Ig = immunoglobulin; RBC = red blood cells; SSA/Ro = Sjögren’s-Syndrome-related antigen A; SSB/La = 
Sjögren syndrome type B antigen/Lupus La protein; WBC = white blood cells.
a
All labs will be assayed/calculated by a Lilly-designated laboratory unless otherwise noted.
b
Unscheduled blood chemistry hematology, and urinalysis panels may be performed at the discretion of the 
investigator.
c
eGFR for serum creatinine will be calculated by the central laboratory using the Modification of Diet in Renal 
Disease (MDRD) isotope dilution mass spectrometry traceable method.
d
Fasting laboratory values for glucose and lipids will be required at baseline, Weeks 12, 24, 48, 108 and 156.  
Patients should not eat or drink anything except water for 12 hours prior to test.  If a patient attends these visits in 
a nonfasting state, this will not be considered a protocol violation.
e
Differential and blood smear may be performed if necessary.
f
Lipid panel consists of direct HDL-C, triglycerides, cholesterol, and LDL-C (calculation from Friedewald et al. 
1972).
g
For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at each study 
visit per the Schedule of Activities.
h
Microscopic examination of sediment will be performed if abnormalities are noted on the routine urinalysis.
i
HBV DNA testing will be performed in patients who tested positive for HBcAb in the originating study

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Appendix 3.
Study Governance Considerations

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

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

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
Review and evaluate CRF data and use standard computer edits to detect errors in 
data collection

Conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1.
Data Capture System
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site into the sponsor-provided electronic data capture system.
Electronic patient-reported outcome (ePRO) measures (e.g., a rating scale) and electronic clinical 
outcome assessments (eCOAs) are entered into an ePRO/eCOA instrument at the time that the 
information is obtained.  In these instances where there is no prior written or electronic source 
data at the site, the ePRO/eCOA instrument record will serve as the source.
If ePRO/eCOA records are stored at a third party site, investigator sites will have continuous 
access to the source documents during the study and will receive an archival copy at the end of 
the study for retention.
Any data for which the ePRO/eCOA instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file.
Case report form data collected by a third-party will be encoded by the third-party and stored 
electronically in the third-party’s database system.  Validated data will subsequently be 
transferred to the sponsor’s data warehouse, using standard Lilly file transfer processes.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse. 
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Appendix 3.3.
Study and Site Closure
Appendix 3.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.

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Appendix 3.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
Appendix 3.4.
Publication Policy
The publication policy for Study I4V-MC-JAIM is described in the Clinical Trial Agreement.

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

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

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

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Amendment Summary for Protocol I4V-MC-JAIM Amendment (a)
Section # and Name
Description of Change
Brief Rationale
Table JAIM.2. – Objectives and Endpoints
Secondary endpoints describing the proportion of 
patients receiving prednisone at baseline able to 
decrease dose by a specified amount that is 
maintained for at least 12 weeks through Week 156 
and the proportion of patients taking corticosteroids 
at baseline able to discontinue use through 
Week 156 were removed.  
It was determined that these categorical endpoints 
were not appropriate for such a long-term study.  
Section 2 - Schedule of Activities 
Several assessments and study visits were removed:

Study visits (V) V8, V10, V12, and V14 
have been removed.

Iron assessments for V1, V6 and V15 have 
been removed.

Autoantibodies (anti-Sm/RNP/SSA/SSB)
assessments for V4 have been removed.

Anti-cardiolipins assessments for V3, V4, 
V5, V7, V9 (now V8), V11 (now V9), and 
V13 (now V10) have been removed.

Anti-beta2 glycoprotein-I assessments for
V3, V4, V5, V7, V9 (now V8), V11 (now 
V9), and V13 (now V10), have been 
removed.

Lupus anticoagulant assessments for V3, 
V4, V5, V7, V9 (now V8), V11 (now V9),
and V13 (now V10), have been removed.
Clarified that both the C-SSRS and Self-Harm 
Supplemental Form are completed at each visit.
To reduce patient burden with less study visits and 
venipuncture, assessments that are unlikely to 
produce additional meaningful data beyond what is 
already known for baricitinib were removed.
Added text to clarify that both the C-SSRS and 
Self-Harm Supplemental Form are required to 
reduce risk for missing data. 
Section 5.1 – Figure JAIM.1.
Figure was updated to remove visits as above.
Updated to be consistent with updated Schedule of 
Activities.
Section 6.1 – Inclusion Criteria 
Hormonal contraception dosage forms were 
corrected from oral, intravaginal, or transdermal to 
oral, injectable, or implantable
Updated to correct a typographical error
Section 7.1.1 - Packaging and Labelling
It was clarified that patients will be instructed to 
Text was clarified to minimize potential risk for 

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take 2 tablets, 1 tablet from 2 different bottles, each 
day.
errors
Section 7.2.1 – Selection and Timing of Doses
Text specifying 1 tablet from each bottle was 
removed.
Text was removed to reduce potential confusion 
particularly at longer visit intervals when more than 
2 bottles of study drug may be provided.
Section 7.3 - Blinding
Text was added to include site personnel and 
patients and to specify the continuation of the blind 
relative to additional trials
Text was added to specify that site personnel and 
patients would remain blinded after database lock 
of trials JAHZ and JAIA

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Amendment Summary for Protocol I4V-MC-JAIM Amendment (a)
Section # and Name
Description of Change
Brief Rationale
Section 8.1.1 - Temporary Interruption of 
Investigational Product; Table JAIM.4. Criteria for 
Temporary Interruption of Investigational Product
Delete interruption criterion based on eGFR <30.
Because of study blinding, “baseline” eGFR will 
not be known to investigators (For patients assigned 
to baricitinib in originating study, eGFR from 
baseline in the originating study is used.  For 
patients assigned to placebo in originating study, 
eGFR from baseline in JAIM is used). The more 
conservative criteria (eGFR <40) will be used.
Section 9.4.6 - Hepatitis B Virus (HBV) DNA 
Monitoring
Text was modified to describe HBV monitoring 
every 6 months after W60.
Text was added to account for the increased 
interval of HBV testing after Week 60 due to the 
removal of study visits V8, V10, V12, and V14.
Section 10.3.1 – General Statistical Considerations
Text was updated to include efficacy and specify 
that integrated data will be assessed.
Updated to clarify that the safety and efficacy data 
would be (in addition to) assessed in the context of 
integrated data
Section 10.3.3 – Efficacy Analyses
Wording was updated to include the ANCOVA 
model.
ANCOVA model was needed to analyze 
SLICC/ACR responses.
Section 10.3.3.1 – Missing Data Imputation
Last Observation Carried Forward was changed to 
Modified Last Observation Carried Forward.
Text was changed to specify the methodology used 
in which to impute missing data.
Section 10.3.4 – Safety Analyses
Text added specifying how the endpoints of safety 
and tolerability would be analyzed and to outline 
safety measures to be reported specifically for 
JAIM.
To specify that the primary endpoints would be 
analyzed as a part of the integrated safety analyses 
for SLE and as such, will be reflected in the 
integrated safety analysis plan for SLE and to 
outline the categorical safety measures to be 
reported specifically for JAIM.  
Section 10.3.4.1 – Adverse Events
PSAP analysis was removed
PSAP and iSAP are redundant terminology.
Section 10.3.4.3 - Vital Signs, Physical Findings, 
and Other Safety Evaluation
Text specifying that further analysis will be planned 
in the SAP iSAP was removed
Upon review of the section, the text was deemed 
unnecessary and was removed.

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

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1.
Synopsis
Objectives and Endpoints

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Table JAIM.1.
Schedule of Activities
Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V98
V10
V119
V12
V131
0
V14
V151
1
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W72
W84
W96
W108
W120
W132
W144
W156
Any
W160 or 
last dose + 
4 weeks
Study Day
1
29 
± 4
85 ± 
7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
505 
± 14
589 
± 14
673 
± 14
757 ± 
± 14
841 ± 
± 14
925 ± 
± 14
1009 
± 14
1093 
± 14
Any
Last dose 
+ 28 ± 5 
days
Procedure
Informed consent
X
Abbreviated patient 
demographics
X
Symptom-directed 
physical examination
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Waist circumference  
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BPd, 
pulse, temperature)
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review JAIM 
inclusion/exclusion 
criteria 
X
Adverse events
Xe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications
Xf
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C-SSRSg & /Self-
Harm Supplement 
Form
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up 
Formh
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16 i
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAIM(a) Clinical Protocol
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Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V98
V10
V119
V12
V131
0
V14
V151
1
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W72
W84
W96
W108
W120
W132
W144
W156
Any
W160 or 
last dose + 
4 weeks
Study Day
1
29 
± 4
85 ± 
7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
505 
± 14
589 
± 14
673 
± 14
757 ± 
± 14
841 ± 
± 14
925 ± 
± 14
1009 
± 14
1093 
± 14
Any
Last dose 
+ 28 ± 5 
days
Log in IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomizationj
X
Investigational 
product dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigational 
product returned and 
compliance assessed
Xk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician-Completed Scalesl
SLEDAI-2K
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BILAG2004
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global 
Assessment of 
Disease Activity
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SLEDAI Flare Index
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SLICC Damage 
Index
Xc
X
X
X
X
X
CLASI
Xc
X
X
X
X
X
X
X
X
X
X
X
X
28-Tender and 
Swollen Joint Counts
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient-Reported Questionnaires
Worst Pain NRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Joint Pain 
NRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Worst Fatigue NRSi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

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Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V98
V10
V119
V12
V131
0
V14
V151
1
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W72
W84
W96
W108
W120
W132
W144
W156
Any
W160 or 
last dose + 
4 weeks
Study Day
1
29 
± 4
85 ± 
7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
505 
± 14
589 
± 14
673 
± 14
757 ± 
± 14
841 ± 
± 14
925 ± 
± 14
1009 
± 14
1093 
± 14
Any
Last dose 
+ 28 ± 5 
days
Patient’s Global 
Impression of 
Severity (PGI-S)i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SF-36v2i
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
FACIT-Fatiguei
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
WPAI-Lupusi
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EQ-5D-5Li
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
HBV DNAm
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy 
testn
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical chemistryo
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Fasting lipid panelp
Xc
X
X
X
X
X
X
X
X
Hematology
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Iron studies (iron, 
TIBC, and ferritin)
Xc
X
X
X
Urinalysis
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Creatinine and 
Protein, Ratio
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ANA
Xc
X
X
X
Anti-dsDNA
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

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Baseline
Treatment Phase: Study Drug Administration
Follow-up
Visit Number
V1
V2
V3
V4
V5
V6
V7
V8
V98
V10
V119
V12
V131
0
V14
V151
1
ETa
V801b
Study Week
W0
W4
W12
W24
W36
W48
W60
W72
W84
W96
W108
W120
W132
W144
W156
Any
W160 or 
last dose + 
4 weeks
Study Day
1
29 
± 4
85 ± 
7
169 
± 10
253 
± 10
337 
± 10
421 
± 10
505 
± 14
589 
± 14
673 
± 14
757 ± 
± 14
841 ± 
± 14
925 ± 
± 14
1009 
± 14
1093 
± 14
Any
Last dose 
+ 28 ± 5 
days
Autoantibodies (anti-
Smith, anti-RNP, 
anti-SSA/Ro, anti-
SSB/La)
Xc
X
X
X
X
X
X
Anti-cardiolipin 
antibodies IgG, IgA, 
IgM)
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Anti-beta2 
glycoprotein-I (IgG, 
IgM) 
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Lupus anticoagulant 
(dRVVT)
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complement (C3 and 
C4)
Xc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunoglobulins 
(IgG, IgA, IgM)
Xc
X
X
X
X
X
Lymphocyte subsets 
(T, B, NK, and T-cell 
subsets)
Xc
X
X
X
X
X
Exploratory storage 
samples (serum and 
plasma)
Xc
X
X
X
X
Exploratory storage 
samples (urine)
Xc
X
X
X
X

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Abbreviations:  ANA = antinuclear antibody; BILAG = British Isles Lupus Assessment Group; BP = blood pressure; CLASI = Cutaneous Lupus Erythematosus 
Disease Area and Severity Index; C-SSRS = Columbia-Suicide Severity Rating Scale; dRVVT = Dilute Russell’s Viper Venom Time; dsDNA = double-
stranded deoxyribonucleic acid; EQ-5D-5L = 5-level EuroQol-5 Dimensions; ET = early termination; FACIT = Functional Assessment of Chronic Illness 
Therapy; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBV DNA = hepatitis B virus deoxyribonucleic acid; 
Ig = immunoglobulin; IWRS = interactive web-response system; NK = natural killer; NRS = numerical rating scale; PGI-S = Patient’s Global Impression of 
Severity; RNP = ribonucleoprotein; QIDS-SR16  =16-Item Quick Inventory of Depressive Symptomatology-Self Report; SF-36v2 = Short-Form 36-item 
Health Survey version 2; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000; 
SLICC = Systemic Lupus Erythematosus International Collaborating Clinics; SSA/Ro = Sjögren’s-Syndrome-related antigen A; SSB/La = Sjögren syndrome 
type B antigen/Lupus La protein; TIBC = total iron binding capacity; V = visit; W = week; WPAI = Work Productivity and Activity Impairment.
a
Patients who discontinue from investigational product (IP) early should complete the ET visit and proceed to post-treatment follow-up.
b
All patients should return for Visit 801, a post-treatment follow-up visit, 28±5 days after the last dose of IP. Patients who discontinue IP but remain in the 
study for at least 28±5 days without IP, can combine their Visit 1115/ET with their Visit 801 (post-treatment follow-up visit).
c
Visit 1 of Study JAIM should occur on the same day as the final visit of the originating study.  Assessments/procedures required for both Visit 1 of Study 
JAIM and the final visit of the origination study should only be performed once.
d
At each time point, 3 replicate readings should be made at approximately 30- to 60-second intervals. Blood pressure is recorded as the average of these 3
readings. A single pulse measurement should be made simultaneously with at least 1 of the readings at each time point (Section 9.4.1. for details on vital 
signs).
e
Adverse events that are ongoing at the completion of the originating trial should be reported as pre-existing conditions at Visit 1 for Study JAIM. 
f
Concomitant medications ongoing at the completion of the originating trial should be reported as concomitant medications at Visit 1 for Study JAIM.
g
Suicidal ideation and behavior subscales excerpt; adapted for the assessment of 11 preferred ideation and behavior categories.  C-SSRS and Self-Harm 
Supplemental Form should be completed after collection of unsolicited adverse events.
h
The Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form.
i
Patient-reported questionnaires will be administered via an on-site electronic clinical outcome assessment (eCOA) device and should be administered prior to 
any clinical assessments.  
j
At Visit 1, patients randomized to active treatment during the originating study will be assigned to the same, blinded dose of baricitinib in Study JAIM.  
Patients randomized to placebo during the originating study will be randomized 1:1 to blinded baricitinib 2-mg or baricitinib 4-mg.  Dose adjustment for 
patients newly randomized to baricitinib, if necessary, will be based on the last available estimated glomerular filtration rate (eGFR) from the originating 
study.
k
New bottles of study drug tablets will NOT be dispensed at Week 4 (Visit 2) unless the patient requires additional tablets for the next visit window.  Patients 
will continue to take tablets from the bottles dispensed at Week 0 (Visit 1).  Compliance will be checked, and the bottles with remaining tablets will be 
returned to the patient for dosing the following visit window.  If new bottles are required, the patient will not have their previous bottles returned.
l
SLE assessments must be completed by a physician and will be documented on an eCOA (electronic clinical outcome assessment) device.
m Patients who were enrolled in the originating study with positive HBcAb and negative HBV DNA, regardless of HBsAb status or level, must undergo HBV 
DNA testing per the schedule of events (see Section 9.4.6 for details of HBV DNA monitoring).

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n
For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at all study visits.  If required per local regulations and/or 
institutional guidelines, pregnancy testing can occur more frequently during the study treatment period.  Unscheduled urine pregnancy tests may also be 
performed if a regular monthly menstruation is absent in a woman of childbearing potential. 
o
Clinical chemistry will include the following value calculated from serum creatinine:  eGFR (calculated using the Modification of Diet in Renal Disease 
[MDRD] isotope dilution mass spectrometry traceable method).
p
Patients should not eat or drink anything, except water, for 12 hours prior to sample collection. If a patient attends these visits in a nonfasting state, the 
sample should still be collected.  This will not be considered a protocol violation.

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5.1.
Overall Design
…
…
6.1.
Inclusion Criteria
…
Patient Characteristics
…

Progestogen-only containing hormonal contraception associated with 
inhibition of ovulation:  oral, intravaginal injectable, or transdermal 
implantable
7.1.1. Packaging and Labelling
…
Patients will be instructed to take 2 tablets, 1 tablet from 2 different each bottles, each day.
All investigational products will be stored, inventoried, reconciled, and destroyed according to 
applicable regulations.  Investigational products will be supplied by Lilly or its representative in 
accordance with current Good Manufacturing Practices and will be supplied with lot numbers, 
expiry dates, and certificates of analysis (as applicable).
7.2.1. Selection and Timing of Doses

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Investigational product will be provided to patients at Visit 1.
Two tablets (1 tablet from each bottle) should be taken orally each day, without regard to food 
and, if possible, at approximately the same time every day.
7.3.
Blinding
This is a double blind study.  After database lock of trials JAHZ and JAIA, site personnel and 
patients will remain blinded to treatment assignment. To preserve the blinding of the study, a 
minimum number of Lilly personnel who are not directly involved with investigational sites will 
see the randomization table and treatment assignments before the study is complete.
8.1.1. Temporary Interruption of Investigational Product
…
Table JAIM.4.
Criteria for Temporary Interruption of Investigational Product
Hold Investigational Product if the Following 
Abnormalities Occur:
Investigational Product May be Resumed When:
WBC count <2000 cells/µL
(<2.00 x 103/µL or <2.00 GI/L)
WBC count 2500 cells/µL
(≥2.50 x 103/µL or ≥2.50 GI/L)
ANC <1000 cells/L 
(<1.00 x 103/µL or <1.00 GI/L)
ANC ≥1200 cells/µL
(≥1.2 x 103/µL or ≥1.2 GI/L)
Lymphocyte count <300 cells/µL
(<0.30 x 103/µL or <0.30 GI/L)
Lymphocyte count 500 cells/µL
(≥0.50 x 103/µL or ≥0.50 GI/L)
Platelet count <25,000/µL
(<25 x 103/µL or <25 GI/L)
Platelet count 50,000/µL
(≥50 x 103/µL or ≥50 GI/L)
eGFR <40 mL/min/1.73 m2 for patients with eGFR 
≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 for patients with eGFR 
≥40 to <60 mL/min/1.73 m2
eGFR 40 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
Infection that, in the opinion of the investigator, 
merits the IP being withhelda
Resolution of infection that, in the opinion of the 
investigator, merits the IP being restarted
Abbreviations:  ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; WBC = white blood cell.
a
Permanent discontinuation of IP should be considered for patients who develop a serious infection that, in the 
opinion of the investigator, would pose an unacceptable risk if IP were resumed.

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9.4.6. Hepatitis B Virus (HBV) DNA Monitoring
Patients who were hepatitis B core antibody positive at screening for the originating study will 
continue to require Hepatitis B virus (HBV) DNA monitoring approximately every 3 months up 
to Week 60, thereafter reducing to every 6 months, regardless of their hepatitis B surface 
antibody status.
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee. A detailed 
SAP describing the statistical methodologies will be developed by Lilly or its designee.
Depending on the efficacy and health outcomes analysis, baseline may be defined as the last 
assessment prior to the first dose of active study drug in Study JAIM or as baseline from the 
originating study.  Depending on the analysis, treatment groups can be based on assignment in 
JAIM, or could be further subdivided based on treatment group assignment in the originating 
studies.
Some of the efficacy and safety endpoints may be better assessed in the context of combining the 
safety data integrating data from the originating studies (and possibly other relevant studies).  
The SAP for this study and the integrated SAPs which specify integrated analyses, (iSAP; which 
will detail how all Phase 2 and 3 studies will be combined) will include details of which analyses 
will be performed on JAIM alone and which will be performed in an integrated fashion 
(including originating studies and possibly other studies).  The exact definition of baseline, 
safety population populations, and treatment groups will depend on the particular analysis 
(integrated vs. JAIM alone).  
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated. Adjustment for multiple comparisons will not be made.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.
10.3.3. Efficacy Analyses
Efficacy and health outcomes analyses will generally be summarized using descriptive statistics.  
The number and percentage of patients maintaining or achieving a categorical efficacy or health 
outcomes response will be summarized.  The mean change from baselines of the continuous 
measures will be summarized using mixed model repeated measures (MMRM), except for 
SLICC/ACR which will be analyzed using analysis of covariance (ANCOVA)mixed model 
repeated measures.  The MMRM model will include treatment, region, visit, treatment-by-visit 
interaction as fixed categorical effects, and baseline value and baseline value-by-visit interaction 

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as fixed continuous effects to estimate change from baseline across postbaseline visits.  
Additional factors, such as originating study (JAHZ, JAIA) and originating study stratification 
factors, may also be included in the model.  The ANCOVA model for analyzing SLICC/ACR 
will be based on the same model factors as the MMRM analyses, excluding visit and value-by-
visit interaction terms.  Additional details, including any outcomes that will utilize statistical 
inference and use of originating study data, will be provided in the JAIM SAP or the integrated 
efficacy analysis plan (IEAP), which will define how the efficacy and health outcomes data from
the Phase 2 and 3 studies will be analyzed when combined.
10.3.3.1.
Missing Data Imputation
Missing data will be imputed at specified time points utilizing methodologies, including the 
following:

Modified Last Observation Carried Forward:  The last observed value (non-
missing value) is used to fill in missing values at a later time point.

Nonresponder imputation:  Patients who discontinue treatment early will be 
defined as nonresponders.
The SAP will stipulate which methodology will be utilized for specific analyses.
10.3.4. Safety Analyses
Safety assessments will include AEs, laboratory analytes, vital signs, and questionnaires to 
assess the existence and severity of depression.
The primary endpoints of safety and tolerability will be analyzed as part of the integrated safety 
analyses for SLE.  All details of these integrated analyses will be contained in the integrated 
safety analysis plan for SLE. 
The cCategorical safety measures for JAIM alone will be summarized with percentages, and 
incidence rates where appropriate. The following events will be reported specifically for JAIM:

patients who permanently discontinue from study drug due to adverse events, 

patients reporting SAEs during the treatment period, 

patients with at least 1 temporary interruption of study drug

patients who permanently discontinued study drug prior to full study completion
The mean changes of the continuous safety measures will be summarized using descriptive 
statistics.  Shift tables for select categorical safety analyses (for example, ‘high’ or ‘low’ 
laboratory results) will also be produced. Additional details, including any measures that will 
utilize inferential statistics will be specified in the SAP and/or, program safety analysis plan
(PSAP) or iSAP.

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10.3.4.1.
Adverse Events
…
Serious adverse events (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.  Potential AESIs will be identified by a 
standardized MedDRA query or a Lilly-defined MedDRA query.  Details of the AESIs 
(including but not limited to those listed in Section 9.2.2) and analysis will be documented in the
SAP, iSAP or PSAP.
…
10.3.4.3.
Vital Signs, Physical Findings, and Other Safety Evaluation
…
The incidence and average duration of investigational product interruptions will be summarized 
and compared descriptively among treatment groups.  Various techniques may be used to 
estimate the effects of investigational product interruptions on safety measures.  
Further analyses may be performed and will be planned in the SAP or iSAP.
Appendix 1
Abbreviations and Definitions
ANCOVA
analysis of covariance
MMRM
mixed model repeated measures

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Appendix 2
Clinical Laboratory Testsa
Hematologyb
Clinical Chemistryb
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Absolute reticulocyte count
Total bilirubin
Mean cell volume (MCV)
Direct bilirubin
Mean platelet volume
Alkaline phosphatase (ALP)
Mean cell hemoglobin (MCH)
Alanine aminotransaminase (ALT)/serum glutamic pyruvic 
transaminase
Mean cell hemoglobin concentration 
(MCHC) Leukocytes (WBC)
Aspartate aminotransferase (AST)/serum glutamic 
oxaloacetic transaminase 
Absolute count of 
Neutrophils, segmented
Blood urea nitrogen (BUN)
Neutrophils, juvenile (bands)
Creatinine
Lymphocytes
Estimated glomerular filtration rate (eGFR)c
Monocytes
Uric acid
Eosinophils
Calcium
Basophils
Glucosed
Platelets
Albumin
Cell morphology
Creatine phosphokinase (CPK)
Differential and blood smeare
Total protein
Lymphocyte subsets (T, B, NK, and T-cell 
subsets)
Iron studies (iron, TIBC, and ferritin)
Lipid Profiled,f
Total cholesterol
Urinalysisb
High-density lipoprotein cholesterol (HDL-C)
Color
Low-density lipoprotein cholesterol (LDL-C)
Specific gravity
Triglycerides 
pH
Urine Protein
Glucose
Other Tests
Ketones
Urine pregnancy test (females only)g
Blood
HBV DNAi
Bilirubin
Serum immunoglobulins (IgG, IgA, IgM)
Urobilinogen
Stored serum, plasma, and urine samples for exploratory 
biomarker analyses
Leukocyte esterase
Lupus anticoagulant (dRVVT)
Nitrite
Complement C3 and C4
Microscopic examination of sedimenth
Anti-beta2 glycoprotein-I (IgG, IgM)
Urine creatinine
Urine protein
Urine protein-creatinine ratio

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Autoantibodies
Anti-nuclear antibody (ANA)
Anti-double-stranded DNA (anti-dsDNA) 
antibody
Autoantibodies (anti-RNP, anti-Sm, anti-
SSA/Ro, anti-SSB/La)
Anti-cardiolipin antibodies IgG, IgA, IgM
Abbreviations:  anti-dsDNA = anti-double-stranded deoxyribonucleic acid; dRVVT = Dilute Russell’s Viper Venom 
Time; HBcAb = hepatitis B core antibody; HBV DNA = hepatitis B virus deoxyribonucleic acid; Ig = 
immunoglobulin; NK = natural killer; RBC = red blood cells; SSA/Ro = Sjögren’s-Syndrome-related antigen A; 
SSB/La = Sjögren syndrome type B antigen/Lupus La protein; TIBC = total iron binding capacity; WBC = white 
blood cells.
a
All labs will be assayed/calculated by a Lilly-designated laboratory unless otherwise noted.
b
Unscheduled blood chemistry hematology, and urinalysis panels may be performed at the discretion of the 
investigator.
c
eGFR for serum creatinine will be calculated by the central laboratory using the Modification of Diet in Renal 
Disease (MDRD) isotope dilution mass spectrometry traceable method.
d
Fasting laboratory values for glucose and lipids will be required at baseline, Weeks 12, 24, 48, 108, 72, 96, 120
and 156.  Patients should not eat or drink anything except water for 12 hours prior to test.  If a patient attends 
these visits in a nonfasting state, this will not be considered a protocol violation.
e
Differential and blood smear may be performed if necessary.
f
Lipid panel consists of direct HDL-C, triglycerides, cholesterol, and LDL-C (calculation from Friedewald et al. 
1972).
g
For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at each study 
visit per the Schedule of Activities.
h
Microscopic examination of sediment will be performed if abnormalities are noted on the routine urinalysis.
i
HBV DNA testing will be performed in patients who tested positive for HBcAb in the originating study