A Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients With Moderate to Severe Atopic Dermatitis
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

Protocol I4V-MC-JAIX(c) 
 
 
A Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in 
Adult Patients with Moderate to Severe Atopic Dermatitis 
 
NCT03559270 
 
Approval Date: 28-Oct-2019 
 
 

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Protocol I4V-MC-JAIX(c)
A Multicenter, Open-Label, Phase 3 Study to Evaluate the 
Efficacy and Safety of Baricitinib in Adult Patients with 
Moderate to Severe Atopic Dermatitis 
BREEZE-AD6
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
baricitin b (LY3009104), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Baricitinib (LY3009104)
Study I4V-MC-JAIX is a Phase 3, multicenter, open-label, outpatient, 204-week study 
designed to evaluate the efficacy and safety of baricitinib 2-mg in patients with moderate to 
severe atopic dermatitis.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly on 08 February 2018.
Amendment (a) Electronically Signed and Approved by Lilly on 9 July 2018.
Amendment (b) Electronically Signed and Approved by Lilly on 1 April 2019.
Amendment (c) Electronically Signed and Approved by Lilly on approval date provided 
below
Approval Date: 28-Oct-2019 GMT

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Table of Contents
Section
Page
Protocol I4V-MC-JAIX(c) A Multicenter, Open-Label, Phase 3 Study to 
Evaluate the Efficacy and Safety of Baricitinib in Adult Patients with 
Moderate to Severe Atopic Dermatitis.................................................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................8
2.
Schedule of Activities .......................................................................................................11
3.
Introduction ......................................................................................................................14
3.1.
Background..................................................................................................................14
3.2.
Study Rationale............................................................................................................15
3.3.
Benefit/Risk Assessment..............................................................................................16
4.
Objectives and Endpoints..................................................................................................18
5.
Study Design.....................................................................................................................19
5.1.
Overall Design .............................................................................................................19
5.1.1.
Period 1:  Open-Label Treatment, Weeks 0 to 200 ...............................................20
5.1.2.
Period 2:  Post-Treatment Follow-Up...................................................................21
5.2.
Number of Participants.................................................................................................21
5.3.
End of Study Definition ...............................................................................................22
5.4.
Scientific Rationale for Study Design...........................................................................22
5.5.
Justification for Dose ...................................................................................................22
6.
Study Population...............................................................................................................23
6.1.
Inclusion Criteria..........................................................................................................23
6.2.
Exclusion Criteria ........................................................................................................24
6.3.
Lifestyle Restrictions....................................................................................................25
6.4.
Screen Failures.............................................................................................................25
7.
Treatments........................................................................................................................26
7.1.
Treatments Administered .............................................................................................26
7.1.1.
Packaging and Labeling .......................................................................................26
7.2.
Method of Treatment Assignment ................................................................................26
7.2.1.
Selection and Timing of Doses.............................................................................26
7.3.
Blinding .......................................................................................................................26
7.4.
Dosage Modification....................................................................................................27
7.5.
Preparation/Handling/Storage/Accountability...............................................................27
7.6.
Treatment Compliance .................................................................................................27
7.7.
Concomitant Therapy...................................................................................................27

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7.7.1.
Prohibited Medications and Procedures................................................................28
7.7.2.
Permitted Medications and Procedures.................................................................29
7.7.3.
Rescue Therapy....................................................................................................29
7.8.
Treatment after the End of the Study............................................................................30
7.8.1.
Continued Access.................................................................................................30
8.
Discontinuation Criteria ....................................................................................................31
8.1.
Discontinuation from Study Treatment.........................................................................31
8.1.1.
Temporary Interruption from Investigational Product...........................................31
8.1.2.
Permanent Discontinuation from Investigational Product .....................................33
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................34
8.2.
Discontinuation from the Study....................................................................................34
8.3.
Lost to Follow-Up........................................................................................................35
9.
Study Assessments and Procedures ...................................................................................36
9.1.
Efficacy Assessments...................................................................................................36
9.1.1.
Primary Efficacy Assessments .............................................................................36
9.1.2.
Secondary Efficacy Assessments..........................................................................36
9.1.2.1.
Validated Investigator’s Global Assessment for Atopic 
Dermatitis (vIGA-AD)....................................................................................36
9.1.2.2.
Eczema Area and Severity Index scores..........................................................36
9.1.2.3.
SCORing Atopic Dermatitis ...........................................................................36
9.1.2.4.
Hospital Anxiety Depression Scale.................................................................37
9.1.3.
Health Outcomes and Quality-of-Life Measures...................................................37
9.1.3.1.
Patient-Oriented Eczema Measure ..................................................................37
9.1.3.2.
Itch Numeric Rating Scale..............................................................................37
9.1.3.3.
Atopic Dermatitis Sleep Scale ........................................................................37
9.1.3.4.
Skin Pain Numeric Rating Scale .....................................................................37
9.1.3.5.
Patient Global Impression of Severity.............................................................38
9.1.3.6.
Dermatology Life Quality Index.....................................................................38
9.1.3.7.
European Quality of Life–5 Dimensions–5 Levels..........................................38
9.1.3.8.
Work Productivity and Activity Impairment 
Questionnaire–Atopic Dermatitis....................................................................38
9.1.4.
Appropriateness of Assessments ..........................................................................39
9.2.
Adverse Events ............................................................................................................39
9.2.1.
Serious Adverse Events........................................................................................39
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................40
9.2.2.
Adverse Events of Special Interest .......................................................................41
9.2.3.
Complaint Handling.............................................................................................41
9.3.
Treatment of Overdose.................................................................................................41

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9.4.
Safety...........................................................................................................................41
9.4.1.
Vital Signs ...........................................................................................................41
9.4.2.
Physical Exam .....................................................................................................41
9.4.3.
Laboratory Tests ..................................................................................................41
9.4.4.
Columbia Suicide Severity Rating Scale...............................................................42
9.4.5.
Self-Harm and Follow-Up Supplement Forms......................................................42
9.4.6.
Hepatitis B Virus DNA Monitoring......................................................................42
9.4.7.
Hepatic Safety Monitoring and Data Collection....................................................43
9.4.8.
VTE Assessment..................................................................................................43
9.4.9.
Safety Monitoring ................................................................................................43
9.5.
Pharmacokinetics .........................................................................................................44
9.6.
Pharmacodynamics ......................................................................................................44
9.7.
Pharmacogenetics.........................................................................................................44
9.8.
Biomarkers...................................................................................................................44
9.9.
Medical Resource Utilization and Health Economics ...................................................45
10.
Statistical Considerations ..................................................................................................46
10.1. Sample Size Determination ..........................................................................................46
10.2. Populations for Analyses..............................................................................................46
10.3. Statistical Analyses ......................................................................................................46
10.3.1.
General Statistical Considerations ........................................................................46
10.3.2.
Descriptive Population Analyses ..........................................................................47
10.3.2.1.
Patient Disposition..........................................................................................47
10.3.2.2.
Patient Characteristics ....................................................................................47
10.3.2.3.
Concomitant Therapy .....................................................................................47
10.3.2.4.
Treatment Compliance....................................................................................47
10.3.3.
Efficacy Analyses ................................................................................................47
10.3.4.
Safety Analyses....................................................................................................48
10.3.5.
Other Analyses.....................................................................................................48
10.3.5.1.
Health Outcome Measures..............................................................................48
10.3.6.
Interim Analyses..................................................................................................48
10.3.6.1.
Adjudication Committee.................................................................................48
11.
References ........................................................................................................................49
12.
Appendices .......................................................................................................................52

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List of Tables
Table
Page
Table JAIX.1.
Schedule of Activities....................................................................................11
Table JAIX.2.
Objectives and Endpoints...............................................................................18
Table JAIX.3.
Treatment Regimen .......................................................................................26
Table JAIX.4.
Criteria for Temporary Interruption of Investigational Product.......................32

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List of Figures
Figure
Page
Figure JAIX.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIX. ...................20

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................53
Appendix 2.
Clinical Laboratory Tests...............................................................................56
Appendix 3.
Study Governance Considerations..................................................................57
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................60
Appendix 5.
Liver Function Testing and Hepatic Safety Monitoring..................................61
Appendix 6.
Monitoring Tests for Confirmed VTE............................................................62
Appendix 7.
Classification of Potency for Topical Corticosteroids.....................................63
Appendix 8.
Investigator Global Assessment .....................................................................64
Appendix 9.
Protocol   I4V MC JAIX(c) Summary - A Multicenter, Open-Label, 
Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in 
Adult Patients with Moderate to Severe Atopic Dermatitis.............................66

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1.
Synopsis
Title of Study:
A Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients with 
Moderate to Severe Atopic Dermatitis
Rationale: 
Atopic dermatitis (AD) is a pruritic, chronic or chronically relapsing, highly symptomatic inflammatory skin disease 
characterized by excessive T cell activation leading to significant skin infiltration by T cells and dendritic cells 
(Bieber 2010).  Presentation is varied, but includes skin manifestations and pruritus, with associated sleep 
disturbances and subsequent skin infections.  The course of disease includes relapses of varying duration and 
severity.
Baricitinib is an orally available, selective Janus kinase (JAK) inhibitor with potency and selectivity for JAK1 and 
JAK2 and less potency for JAK3 or tyrosine kinase 2 (TYK2) (Fridman et al. 2010).  The pathogenesis of AD is 
thought to be modulated through thymic stromal lymphopoietin (TSLP), interleukin (IL)-13, IL-4, IL-5, IL-22, and 
IL-31, many of which activate receptors with downstream signaling through intracellular JAK1/JAK2/TYK2
(Nomura and Kabashima 2016).  This activity profile suggests that baricitinib would inhibit many of the cytokines 
involved in AD pathogenesis.
Clinical studies have established that baricitinib is effective in autoimmune/autoinflammatory diseases involving the 
joints, kidneys, and skin.  Baricitinib was effective at reducing swollen and tender joints in patients with rheumatoid 
arthritis (Genovese et al. 2016; Dougados et al. 2017; Fleischmann et al. 2017; Taylor et al. 2017); was effective at 
reducing disease severity in patients with moderate to severe plaque psoriasis (Papp et al. 2016); was effective at 
reducing the urinary albumin-to-creatinine ratio in patients with diabetic kidney disease (Tuttle et al. 2015); and in a 
recently completed Phase 2 study (Study I4V-MC-JAHG) was effective at reducing disease severity in patients with 
moderate to severe AD.  The mechanism of action, combined with demonstration of clinical benefit in inflammatory 
diseases involving joints, kidneys, and skin, provides the rationale for evaluating baricitinib in moderate to severe AD.

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Objectives/Endpoints:
Objectives
Endpoints
Primary
To describe the clinical response to baricitinib 2-mg 
QD in patients with moderate to severe AD by prior 
treatment received (ie., baricitinib 2-mg, 1-mg, or 
placebo) and responder status achieved in Study I4V-
MC-JAIW (JAIW).

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at Week 16
Secondary
To describe the clinical response to baricitinib 2-mg 
QD in AD as measured by improvement in signs and 
symptoms of AD by prior treatment received (ie., 
baricitinib 2-mg, 1-mg, or placebo) and responder 
status achieved in Study JAIW.

Proportion of patients achieving IGA of 0 or 1 
assessed at Week 16 

Proportion of patients achieving IGA of 0 or 1 
assessed at or before Week 16

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at or before 
Week 16

Mean percent change from baseline in EASI score 
from baseline of originating study, assessed at 
Week 16 

Proportion of patients achieving a BSA of ≤3% 
assessed at or before Week 16
To describe the clinical response to baricitinib 2-mg 
QD in AD as assessed by patient-reported outcome 
measures by prior treatment received (ie., baricitinib 
2-mg, 1-mg, or placebo) and responder status 
achieved in Study JAIW.

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 
originating study, assessed at Week 16

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 
originating study, assessed at or before Week 16

Mean percent change from baseline of originating 
study, in Itch NRS assessed at Week 16
Abbreviations:  AD = atopic dermatitis; BSA = body surface area EASI = Eczema Area and Severity Index; 
EASI75 = 75% improvement from baseline in EASI; IGA = Investigator’s Global Assessment; NRS = numeric 
rating scale; QD = once daily.
Summary of Study Design:
Study I4V-MC-JAIX (JAIX) is a Phase 3, multicenter, open-label outpatient study evaluating the efficacy and safety 
of baricitinib 2-mg once daily (QD) in adult patients with moderate to severe AD.  The study population will include 
patients 18 years or older with a history of inadequate response or intolerance to existing topical therapies, and who 
have completed protocol-defined minimal participation in Study JAIW based on responder status.
The study duration will be up to 204 weeks over 2 study periods:

Period 1:  Open-Label Treatment Period, lasting from Week 0 (baseline, Visit 1) through Week 200
(Visit 17).

Period 2:  Post-Treatment Follow-Up Period (Visit 801), spanning the period from the last treatment visit at 
Week 200 (Visit 17) or Early Termination Visit (ETV) to approximately 4 weeks following the last dose of 
investigational product.

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Treatment Arms and Duration:
Patients will be assigned at baseline to open-label treatment with baricitinib 2-mg QD.  The study duration will be 
up to 204 weeks (Open-Label Treatment Period:  200 weeks; Post-Treatment Follow-Up Period:  approximately 
4 weeks after the last dose of investigational product).
Number of Patients:
This study will include up to 450 patients with AD who will be treated with baricitinib 2-mg QD.
Statistical Analysis:
Unless otherwise specified, the efficacy and health outcomes summaries will be conducted on all enrolled patients
who receive at least 1 dose of investigational product in Study JAIX, even if the patient does not follow the protocol, 
and safety analyses will be conducted on all enrolled patients who receive at least 1 dose of investigational product
and who do not discontinue from the study for the reason “Lost to Follow-up” at the first postbaseline visit.  
Treatment comparisons of discrete efficacy variables between prior-treatment-received groups may be performed 
using group percentages.    All patients who discontinue the study or study treatment at any time for any reason will 
be defined as nonresponders for the nonresponder imputation (NRI) analysis for categorical variables after 
discontinuation onward.  
Continuous efficacy variables will be descriptively summarized in terms of number of patients, mean, standard 
deviation, median, minimum, and maximum.   
Frequencies and percentages will be computed for adverse event (AE), discontinuation, and other categorical safety 
data.    

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a
Any assessments/procedures conducted during the final visit of the patient’s originating study (Study JAIW) should not be repeated during their first visit 
for Study JAIX.
b An ET visit should be conducted if a patient discontinues from the study before Week 200.  Early termination visit activities do not need to be duplicated 
if occurring at the time of a scheduled visit. Weighing of TCS and collection of HADS, EQ-5D-5L, and WPAI-AD are not to be performed at Study Visit 17; 
these activities should only be performed at the ET visit if it occurs at or before Week 104. 
c
Visit 801 is the PTFU visit, which occurs after the patient has been off baricitinib/IP for approximately 4 weeks.  Patients who have permanently discontinued 
IP but remain in the study for more than 28 days without IP will only complete Visit 17/ET; Visit 801 (follow-up visit) is not required. 
d Screening should occur during the LPV of the originating study.   It may be permissible for screening to occur after the last visit of the originating study 
if needed, upon approval from the sponsor.
e Applies to ET visit if conducted prior to Week 16 only.
f
Only required at investigator discretion. Sponsor provided low potency TCS will be available to dispense to patients at anytime prior to study visit 11.  
At visit 11 and after, low potency TCS is allowed as background therapy but will not be provided by the sponsor or reimbursed by the sponsor.  
g The following measures (POEM, DLQI, HADS, EQ-5D-5L, WPAI-AD) should be completed prior to any clinical assessments being performed on days when 
study visits occur.
h Suicidal ideation and behavior subscales excerptadapted for the assessment of 11 preferred ideation and behavior categories.
i
The Self-Harm Follow-Up Form is required only if triggered by the Self-Harm Supplement Form.
j
Fasting lipid profile.  Patients should not eat or drink anything except water for 12 hours prior to sample collection.  If a patient attends these visits in a 
nonfasting state, this will not be considered a protocol violation.  Unscheduled lipid testing can be performed at the discretion of the investigator.
k If laboratory examinations have been performed ≤4 weeks from previous study visit, then they do not need to be repeated.
l
For ET visits, collect fasting lipids when possible. 
m Clinical chemistry will include the following value calculated from serum creatinine:  estimated glomerular filtration rate (eGFR; calculated using the Chronic 
Kidney Disease Epidemiology Collaboration [CKD-EPI] Creatinine 2009 equation).
n Patients who are positive for HBcAb and negative for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive as determined at screening 
of originating study, Study JAIW, regardless of HBsAb status or level, must undergo HBV DNA testing per the schedule.
o Urinalysis, serum IgE, exploratory storage samples, and RNA and biomarker samples are only collected for ET visits occurring at or before Week 104.  These 
samples are not collected as a component of Visit 17.
p   For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at all specified visits. If required per local regulations 
and/or institutional guidelines, pregnancy testing can occur at other times during the study treatment period.

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3.
Introduction
3.1.
Background
Atopic dermatitis (AD), also known as eczema or atopic eczema, is a common, chronic, 
relapsing, highly symptomatic inflammatory skin disease (Bieber 2010).  Patients with AD may 
present with skin lesions that can be acute with oozing, crusted, eroded vesicles or papules on 
erythematous plaques.  Patients may also present with lesions that have a subacute appearance, 
with thick and excoriated plaques, or chronic appearance, with lichenified, slightly pigmented, 
excoriated plaques (Bieber 2010).  AD causes pruritus attacks throughout the day, which is the 
primary source of morbidity in this disorder (Simpson 2012). Pruritus often leads to an “itch–
scratch” cycle, further compromising the epidermal barrier and resulting in dry skin, microbial 
colonization, and secondary infections (Krakowski et al. 2008), with 36% of patients reporting 
that they often or always scratch until their skin bleeds (Langenbruch et al. 2014). Pruritus from 
AD can worsen at night, resulting in sleep disturbances, with approximately 27% of adult 
patients with AD experiencing sleep disturbance as a result of itching (Langenbruch et al. 2014).
In adult patients with moderate to severe AD, poor sleep quality and latency were significantly 
associated with poor quality of life (Yano et al. 2013).
In clinical practice, AD is classified as mild, moderate, or severe based on a variety of clinical 
features, including severity of skin lesions and pruritus and extent of disease (body surface area 
[BSA] involved).
Until recently, there were no US Food and Drug Administration-approved systemic treatments 
for patients with moderate to severe AD, with the exception of systemic corticosteroids.  In 
March 2017, Dupixent® (dupilumab) injection, an IgG4 monoclonal antibody that inhibits IL-4 
and IL-13, was approved by the US Food and Drug Administration for this patient population.  
In the European Union, only cyclosporine has been approved for the treatment of patients with 
severe AD (Bieber and Straeter 2015).  A recently completed Phase 2 study 
(Study I4V-MC-JAHG [JAHG]) evaluated the safety and efficacy of baricitinib (a JAK inhibitor) 
in AD, and results showed significant improvement in disease severity compared to placebo, and 
no new safety concerns were identified.
In addition to AD, baricitinib has also been studied in Phase 3 in patients with rheumatoid 
arthritis (RA) and in Phase 2 in patients with diabetic nephropathy, moderate to severe psoriasis,
and systemic lupus erythematosus.
Through 13 February 2019, baricitinib has been studied in more than 548 healthy volunteers and 
6555 patients have received baricitinib in clinical studies.  As of 13 February 2018, more than 
2700 patients have been treated with baricitinib for more than a year and more than 1800 patients 
have been treated with baricitinib for more than 2 years at doses of 2-mg once daily or 4-mg 
once daily across the RA clinical program. Baricitinib has been administered as single doses 
ranging from 1- to 40-mg and as repeat oral doses ranging from 2- to 20-mg to healthy 
subjects. Baricitinib has also been administered to patients with RA at doses up to 15-mg daily 
for 4 weeks, 10-mg daily for 24 weeks, 8-mg daily for 76 weeks, and lower doses up to 4-mg 
daily for up to approximately 7 years. 

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3.2.
Study Rationale
The underlying cause of AD is not completely understood.  Loss of function mutations in the 
gene for filaggrin (filament aggregating protein), a key protein in terminal differentiation of the
epidermis contributing to barrier function, has been identified as the strongest genetic risk factor
for AD in European populations (Palmer et al. 2006). At a cellular level, AD is characterized by 
excessive T cell activation caused by genetic and environmental factors, leading to significant 
skin infiltration by T cells and dendritic cells. The cytokine TSLP is thought to act as a master 
switch that triggers the initiation and maintenance of AD (Moniaga et al. 2013; Ziegler et al. 
2013). Overexpression of TSLP in keratinocytes, the most prevalent cell type in the skin, 
triggers robust itch-evoked scratching and the development of an AD-like skin phenotype in 
mice (Li et al. 2005). In addition to directly inducing itch by activating sensory neurons in the 
skin, TSLP also enhances maturation and differentiation of dendritic cells and naive CD4+ 
T cells and induces production of Th2-related cytokines involved in AD pathogenesis (Wilson 
et al. 2013; Divekar and Kita 2015). TSLP and other key cytokines involved in AD 
pathogenesis, such as IL-13, IL-5, IL-22, and IL-31, signal through receptors associated with 
intracellular JAK1/JAK2/TYK2 signaling (Ziegler et al. 2013; Nomura and Kabashima 2016).
JAKs are a family of tyrosine kinases that mediate cytokine receptor signalling through 
phosphorylation and activation of signal transducers and activators of transcription proteins.  
There are 4 known JAK family members:  JAK1, JAK2, JAK3, and TYK2 (Clark et al. 2014).
The relative affinity of JAK inhibitors for different members of the JAK kinase family allows for 
differentiation of JAK inhibitors in relation to their enzymatic inhibitory profile. In vitro assays 
indicate that baricitinib is a selective inhibitor of JAKs with potency and selectivity for JAK1/2 
and less potency for JAK3 or TYK2 (Fridman et al. 2010).  The balanced JAK1/JAK2 inhibitory 
profile of baricitinib suggests that baricitinib will have the greatest modulatory effect in 
cytokines signalling through a JAK1/JAK2 heterodimer intracellularly (or a JAK1/JAK2/TYK2), 
such as IL-6, TSLP, IL-13, or IL-31 (Vaddi and Luchi 2012).
The recently completed Phase 2 study of baricitinib in AD, Study JAHG, met its primary 
objective of proportion of patients achieving a 50% improvement from baseline in Eczema Area 
and Severity Index (EASI50) scores compared to placebo. Baricitinib also showed statistically 
significant improvements for other disease severity analyses as well as multiple different 
patient-reported outcome scales compared to placebo, further validating the hypothesis that 
JAK1/JAK2 signaling plays a key role in AD pathogenesis.  Phase 3 placebo-controlled studies 
are ongoing to define baricitinib efficacy in AD.  This open-label, long-term extension study is 
designed to further assess long-term efficacy and safety of baricitinib in patients with moderate 
to severe AD, who did not achieve Investigator’s Global Assessment [IGA] 0 or 1 in the 
originating study, Study I4V-MC-JAIW (JAIW).  This will allow patients originally randomized 
to baricitinib 1-mg or placebo in Study JAIW to have the opportunity for treatment with 
baricitinib 2-mg QD, and also assess the longer-term clinical utility of the 2-mg dose beyond 
achieving an IGA 0,1.  In addition, this study will give patients completing Study JAIW as 
responders the opportunity for ongoing access to baricitinib 2-mg.

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3.3.
Benefit/Risk Assessment
CCI
CCI
CCI

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Additional information about the known and expected benefits, risks, serious AEs (SAEs), and 
reasonably anticipated AEs of baricitinib can be found in the investigator’s brochure (IB).  
CCI

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4.
Objectives and Endpoints
Table JAIX.2 shows the objectives and endpoints of the study.
Table JAIX.2.
Objectives and Endpoints
Objectives
Endpoints
Primary
To describe the clinical response to baricitinib 2-mg 
QD in patients with moderate to severe AD by prior 
treatment received (ie., baricitinib 2-mg, 1-mg, or 
placebo) and responder status achieved in Study I4V-
MC-JAIW (JAIW)

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at Week 16
Secondary
To describe the clinical response to baricitinib 2-mg 
QD in AD as measured by improvement in signs and 
symptoms of AD by prior treatment received (ie., 
baricitinib 2-mg, 1-mg, or placebo) and responder 
status achieved in Study JAIW.

Proportion of patients achieving IGA of 0 or 1 
assessed at Week 16

Proportion of patients achieving IGA of 0 or 1 
assessed at or before Week 16

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at or before 
Week 16

Mean percent change from baseline in EASI score 
from baseline of originating study, assessed at 
Week 16 

Proportion of patients achieving a BSA of ≤3% 
assessed at or before Week 16
To describe the clinical response to baricitinib 2-mg 
QD in AD as assessed by patient-reported outcome 
measures by prior treatment received (ie., baricitinib 
2-mg, 1-mg, or placebo) and responder status 
achieved in Study JAIW.

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of
originating study, assessed at Week 16

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 
originating study, assessed at or before Week 16

Mean percent change from baseline of originating 
study, in Itch NRS assessed at Week 16
Exploratory Objectives/Endpoints

Exploratory objectives may include evaluating the response to baricitinib treatment regimens on clinical 
measures and patient reported outcomes.  These endpoints may include dichotomous endpoints or change 
from baseline for the following measures:  IGA, EASI, SCORAD, POEM, HADS, DLQI, WPAI-AD, EQ-
5D-5L, Itch NRS, ADSS Item 2 score, Skin Pain NRS, PGI-S-AD.
Abbreviations:  AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BSA = body surface area; DLQI = 
Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; EASI75 = 75% improvement from 
baseline in EASI; EQ-5D-5L = the European Quality of Life–5 Dimensions–5 Levels; HADS = Hospital Anxiety 
Depression Scale; IGA = Investigator’s Global Assessment; NRS = numeric rating scale; QD = once daily; 
PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; POEM = Patient-Oriented Eczema 
Measure; SCORAD = SCORing Atopic Dermatitis; WPAI-AD = Work Productivity and Activity Impairment –
Atopic Dermatitis.

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Abbreviations:  AD = atopic dermatitis; QD = once daily; V = visit; W = week.
a
Occurs approximately 28 days after the last dose of investigational product.
Figure JAIX.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIX.
5.1.1. Period 1:  Open-Label Treatment, Weeks 0 to 200
Screening should occur during the last visit of the originating study. Study eligibility for each 
patient will be reviewed based on all enrollment criteria (Section 6). Patients who meet all 
criteria will have treatment allocated by interactive web-response system (IWRS) and begin their 
treatment period at Visit 1. Patients who meet all of the inclusion and none of the exclusion 
criteria (Section 6) will be enrolled in the study.  It may be permissible for screening to occur
after the last visit of the originating study if needed, upon approval from the sponsor. For 
example, patients requiring elective procedures may want to have those in between studies, or 
responders who complete Visit 15 of Study JAIW have the option to delay enrollment into open-
label Study JAIX to assess response while off investigational product.
Patients who received oral systemic AD treatment and/or topical rescue therapy during the 
originating study must discontinue use of the prohibited medications listed in Section 7.7.1 prior 
to initiating IP in Study JAIX.  Low-potency TCS (e.g., hydrocortisone 2.5% ointment) is 
permitted (Section 7.7.2).
Patients will receive open-label baricitinib 2–mg QD.  Investigational product will be 
administered daily for a maximum of 200 weeks (treatment period Visits 1 through 17; see 
Section 7).  All patients will be required to use emollients daily.  Daily diaries will continue to be 
utilized through Week 16.  Download of this data will be required at study visits.  Patients are 
allowed to use low potency TCS (e.g., hydrocortisone 2.5% ointment) in combination with 
investigational product.  Rescue with higher potency TCS, topical calcineurin inhibitors
(TCNIs), or systemic therapies is not allowed.  Assessments of disease severity will be 
performed by the investigator as described in the Schedule of Activities (Section 2).

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The primary efficacy endpoint will be at Week 16 (Visit 4). All patients who permanently 
discontinue investigational product prior to the primary endpoint should complete an ETV and 
post-treatment follow-up visit.  
At Week 16, all patients should be formally assessed to determine if sufficient clinical benefit 
has been observed to justify continuing in this study.  Clinical benefit is defined as meeting at 
least 1 of the following criteria during the first 16 weeks:

IGA score of 0 or 1 with a ≥2-point improvement from baseline of originating study, 

≥4-point improvement from baseline of originating study in Itch NRS, 

EASI-75 from baseline of originating study, or

BSA involvement of ≤3%. 
If a patient achieves any of these treatment goals during the first 16 weeks of the treatment 
period, the patient will be allowed to continue in the study. Although formal criteria for 
sufficient clinical benefit should be assessed at Week 16, investigators are strongly encouraged 
to discontinue patients who have not shown signs of clinical benefit by Week 8 of Study JAIX, 
defined as improvement in IGA, itch NRS, EASI, or BSA. Attention should be given to patients 
treated continuously for 16 weeks during Study JAIW (no IP discontinuation for systemic rescue 
therapy) and who then show no benefit in Study JAIX, to avoid exposing patients to a potentially 
ineffective therapy for an additional 16 weeks before discontinuation.  Since no rescue therapies 
are available during this study, patients requiring more than low-potency TCS at any time during 
the study will be discontinued.
5.1.2. Period 2:  Post-Treatment Follow-Up
Patients who complete the study through Visit 17 (Week 200) will have a post-treatment
follow-up visit (Visit 801) approximately 28 days after the last dose of investigational product.
Patients who have received at least 1 dose of investigational product and discontinue early from 
the study should have an ETV, and return for the post-treatment safety follow-up visit (Visit 801) 
approximately 28 days after the last dose of investigational product.
Patients who have discontinued investigational product but remain in the study for more than 
28 days without investigational product will have an ETV if they choose to discontinue early; 
however, a separate follow-up visit (V801) is not required.
Patients should not initiate new systemic AD treatment during this period.  However, if patients 
or investigators must initiate treatment, investigators should make every attempt to conduct 
efficacy and safety assessments immediately before administering any new treatment. 
An unscheduled visit can be used for this purpose if necessary. 
5.2.
Number of Participants
Up to 450 participants may be enrolled.

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5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
This open-label long-term extension study will enroll moderate to severe AD patients who have 
completed Visit 8, Week 16 of Study JAIW but who did not achieve IGA 0,1, or who experience 
loss of response after Week 16, or who complete Study JAIW as responders at Visit 15, Week 
104. This study will further assess long-term efficacy and safety of baricitinib in this population.  
This will allow patients originally randomized to baricitinib 1-mg or placebo in Study JAIW to 
have the opportunity for treatment with baricitinib 2-mg QD, and also assess the longer-term 
clinical utility of the 2-mg dose beyond achieving an IGA 0,1.
During the open-label treatment period, patients will be treated with baricitinib 2-mg, which has 
been shown to be efficacious in the Phase 2 study in AD (JAHG). Patients will also be allowed 
to use low-potency TCS (e.g., hydrocortisone 2.5% ointment) as background therapy for comfort 
if needed. Daily treatment with emollient will continue. To avoid confounding effect of topical 
therapies, higher-potency TCS, as well as TCNIs and topical phosphodiesterase type 4 (PDE-4) 
inhibitors are not allowed at any time during the study. If a patient does not experience sufficient 
clinical benefit during the study, the patient should be discontinued.  The criteria for determining 
sufficient clinical benefit are discussed in Section 5.1.1.  This 4-year-long study will generate 
important long-term efficacy and safety data in AD.
The post-treatment follow-up period (Period 2) is for safety monitoring after the patient has been 
off investigational product for approximately 28 days.
5.5.
Justification for Dose
The dose used in Study JAIX is baricitinib 2-mg QD.  This dose was chosen primarily on the 
basis of the recently completed Phase 2 AD study, Study JAHG, and is additionally supported by 
pharmacokinetic, safety, and efficacy data for baricitinib in Phase 2 and Phase 3 RA studies and 
a Phase 2 psoriasis study.
In the Phase 2 Study JAHG, baricitinib 2-mg showed benefit on the clinically important
endpoints (EASI, IGA, SCORAD, POEM, and DLQI) as compared to placebo, and had an 
acceptable safety profile at Week 16.  To ensure that all patients participating in the originating 
study, Study JAIW, have the opportunity to receive the highest dose proposed in the study, this 
open-label study will treat all patients with the 2-mg dose.   

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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
Study investigator(s) will determine if the patient meets all inclusion criteria and none of the 
exclusion criteria to qualify for enrollment in the study.  All screening activities must be 
completed and reviewed before the patient is enrolled.
6.1.
Inclusion Criteria
Type of Patient and Disease Characteristics
[1]
have completed the minimum number of visits based on responder status in 
Study JAIW

nonresponder/partial responder: have completed at least 16 weeks of 
treatment in Study JAIW (i.e., Visit 8, Week 16)
A nonresponder/partial responder is defined as a patient who met at least 1 
of the following in Study JAIW: 

did not achieve an IGA of 0 or 1 at Week 16, or

achieved an IGA ≥3 after Week 16, or

required rescue therapy at any time.
or

responder: have completed the full treatment period of Study JAIW (i.e., 
Visit 15, Week 104)
A responder is defined as a patient who achieved IGA 0 or 1 and who did
not require rescue therapy at or before Week 16 in Study JAIW.
[2]
are able to read, understand, and give documented (electronic or paper 
signature) informed consent.
[3]
are male or nonpregnant, nonbreastfeeding female patients, and
a.
Male patients will either remain abstinent (if this is their preferred and 
usual lifestyle) or agree to use 2 forms of birth control (1 must be highly 
effective, see below) while engaging in sexual intercourse with female 
partners of childbearing potential while enrolled in the study and for at 
least 4 weeks following the last dose of investigational product.
Men who are in exclusively same sex relationships (when it is their 
preferred and usual lifestyle) are not required to use contraception.

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b. Female patients of childbearing 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 males. Periodic abstinence (for example,
calendar, ovulation, symptothermal, post-ovulation methods), declaration 
of abstinence just for the duration of a trial, and withdrawal are not 
acceptable methods of contraception. 
Otherwise, female patients of childbearing potential must agree to use 
2 forms of birth control when engaging in sexual intercourse with a male 
partner while enrolled in the study and for at least 4 weeks following the 
last dose of investigational product.
The following birth control methods are considered acceptable (the patient 
should choose 2 to be used with their male partner, and 1 must be highly 
effective):
o
Highly effective birth control methods: oral, injectable, or implanted 
hormonal contraceptives (combined estrogen/progesterone or 
progesterone only, associated with inhibition of ovulation); 
intrauterine device or intrauterine system (for example,
progestin-releasing coil); or, vasectomized male (with appropriate 
post-vasectomy documentation of the absence of sperm in the 
ejaculate).
o
Effective birth control methods: condom with a spermicidal foam, gel, 
film, cream, or suppository; occlusive cap (diaphragm or cervical/vault 
caps) with a spermicidal foam, gel, film, cream, or suppository; or, 
oral hormonal contraceptives.
Note:  When local guidelines concerning highly effective or effective 
methods of birth control differ from the above, the local guidelines 
must be followed.
c.
Females of nonchildbearing potential are not required to use birth control.
They are defined as:
o
women aged ≥60 years or women who are congenitally sterile, or
o
women aged ≥40 and <60 years who have had a cessation of menses 
for ≥12 months and a follicle-stimulating hormone test confirming 
nonchildbearing potential (≥40 mIU/mL or ≥40 IU/L), or women who 
are surgically sterile (that is, have had a hysterectomy or bilateral 
oophorectomy or tubal ligation).
6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:

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[4]
are currently enrolled in any other clinical trial involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study.
[5]
have significant uncontrolled cerebro-cardiovascular (e.g., myocardial 
infarction [MI], unstable angina, unstable arterial hypertension, severe heart 
failure, or cerebrovascular accident), respiratory, hepatic, renal, 
gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or 
abnormal laboratory values that developed during a previous baricitinib study 
that, in the opinion of the investigator, pose an unacceptable risk to the patient 
if investigational product continues to be administered. 
[6]
have a history of VTE, or are considered at high risk of VTE as deemed by the 
investigator.
[7]
Have a known hypersensitivity to baricitinib or any component of this 
investigational product.
[8]
Had investigational product permanently discontinued at any time during a 
previous baricitinib study, except for patients who had investigational product 
discontinued during originating study because of rescue with an oral systemic 
AD therapy (e.g., corticosteroid, cyclosporine, methotrexate).
[9]
Had temporary investigational product interruption continue 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.
[10] 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.
[11] Are unwilling or unable to comply with the use of a data collection device to 
directly record data from the subject.
6.3.
Lifestyle Restrictions
Not applicable.
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 2-mg administered orally QD.  Table JAIX.3 shows the treatment 
regimen.
Table JAIX.3.
Treatment Regimen
Regimen
Investigational Product Supplied
Dose
Baricitinib 2–mg QD
Baricitinib 2-mg tablet
1 tablet per day
Abbreviation:  QD = once daily.
The investigator or his or her designee is responsible for the following:

explaining the correct use of the investigational agent(s) to the patient

verifying that instructions are followed properly

maintaining accurate records of investigational product dispensing and collection

returning all unused medication to Lilly or its designee at the end of the study,
unless the sponsor and sites have agreed all unused medication is to be destroyed 
by the site, as allowed by local law
7.1.1. Packaging and Labeling
The sponsor (or its designee) will provide the following investigational product:

tablets containing 2-mg of baricitinib
Investigational product tablets will be provided in bottles. Clinical trial materials will be labeled 
according to the country’s regulatory requirements. Patients will be instructed to take 1 tablet 
each day.
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will receive baricitinib 2-mg at Visit 1 (Week 0).  
Site personnel will confirm that they have located the correct bottles by entering the confirmation 
number found on the bottle into an interactive web-response system (IWRS).
7.2.1. Selection and Timing of Doses
The investigational product (1 tablet) should be taken once daily without regard to food and, if 
possible, at approximately the same time every day, usually at the start of the patient’s day, to aid 
patient compliance.  
7.3.
Blinding
This is an open-label study.

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7.4.
Dosage Modification
Not applicable.
7.5.
Preparation/Handling/Storage/Accountability
All investigational product (used and partially used) will be returned to the sponsor or destroyed 
at site level with the sponsor’s written approval.  In some cases, sites may destroy the material if, 
during the investigative site selection, the evaluator has verified and documented that the site has 
appropriate facilities and written procedures to dispose of clinical trial materials.
Follow storage and handling instructions on the investigational product packaging.
7.6.
Treatment Compliance
Patient compliance with study medication will be assessed at each visit during the treatment 
period (Visit 2 through Visit 17) by counting returned tablets.  
A patient will be considered significantly noncompliant if he or she misses more than 20% of the 
prescribed doses of investigational product during the study, unless the patient’s investigational 
product is withheld by the investigator for safety reasons.  Similarly, a patient will be considered 
significantly noncompliant if he or she is judged by the investigator to have intentionally or 
repeatedly taken 20% more than the prescribed amount of medication during the study.
Patients will be counseled by study staff on the importance of taking the investigational product 
as prescribed, as appropriate.
Patients’ compliance will be further defined in the statistical analysis plan (SAP).
7.7.
Concomitant Therapy
All concomitant medication, whether prescription or over the counter, used at baseline and/or
during the course of the study, must be recorded on the Concomitant Medication electronic case 
report form (eCRF).  Patients will be instructed to consult the investigator or other appropriate 
study personnel at the site before taking any new medications or supplements during the study. 
For AD therapies permitted as part of rescue therapy, see Section 7.7.3.

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7.7.1. Prohibited Medications and Procedures
Prohibited Medications and Procedures Not Requiring Interruption of Investigational 
Product
The following therapies will not be allowed during the study. 

Medium-potency TCS or higher potency TCS, TCNIs (for example, tacrolimus and 
pimecrolimus), or topical PDE-4 inhibitor (that is, crisaborole) are not allowed.  
Low-potency TCS is allowed (see Section 7.7.2).

Allergen immunotherapy.

Phototherapy including PUVA (psoralen and ultraviolet A), ultraviolet B, tanning booth 
and excimer laser.

Bleach baths
Prohibited Medications Requiring Temporary Interruption of Investigational Product
The following therapies will not be allowed during the course of the study and, if taken by or 
administered to the patient, temporary interruption of investigational product is required.

Live vaccines (including Bacillus Calmette-Guérin [BCG] or herpes zoster)
o
For BCG vaccination, investigational product should be temporarily interrupted for 
12 weeks.
o
For herpes zoster vaccination, investigational product should be temporarily 
interrupted for 4 weeks. 

Probenecid:  if a patient is inadvertently started on probenecid, investigational product
should be temporarily interrupted and can be resumed after patient has discontinued 
probenecid. If a patient is not able to discontinue probenecid, then investigational 
product should be permanently discontinued.

Systemic corticosteroids may be used for the treatment of an AE (for example, worsening 
of existing condition, such as asthma flare). Investigational product may be restarted if 
systemic corticosteroids were used for a short duration (<30 days).  If used for >30 days, 
sponsor approval to restart investigational product is required.  Systemic corticosteroids 
may not be used to treat AD.

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Prohibited Medications Requiring Permanent Discontinuation of Investigational Product

Any systemic therapy, investigational or commercial (approved or off-label use), used for 
the treatment of AD or symptoms of AD (except for antihistamines, as specified below).

Other JAK inhibitors (for example, tofacitinib and ruxolitinib).

Systemic immunosuppressive/immunomodulatory substances, including, but not limited 
to cyclosporine, methotrexate, mycophenolate mofetil, interferon γ, azathioprine, or 
biologic agents.
7.7.2. Permitted Medications and Procedures
Treatment with concomitant AD therapies during the study is permitted only as described below.

Daily use of emollients is required as background treatment.  Moisturizers with 
additives such as antipruritics or antiseptics are not permitted.  If daily 
applications are missed, it will not be considered a protocol violation.
o
Patients should not apply emollients on the day of their study visit before study 
procedures to allow adequate assessment of skin dryness.

Antihistamines are allowed.

Intra-articular or soft tissue (bursa, tendons, and ligaments) corticosteroid 
injection:  No more than 1 intra-articular or soft tissue (bursa, tendons, and 
ligaments) corticosteroid injection is allowed up until Week 16 (Visit 4).  After 
Week 16, such injections are permitted.  

Intranasal or inhaled steroid use is allowed.

Topical anesthetics and topical and systemic anti-infective medications are 
allowed.

Nonlive seasonal vaccinations and/or emergency vaccination, such as rabies or 
tetanus vaccinations, are allowed.

Low-potency TCS (for example, hydrocortisone 2.5% ointment) is permitted.
o
Patients should not apply TCS on the day of their study visit before study procedures 
to allow adequate assessment of skin dryness.
Any changes of these concomitant medications must be recorded in the Concomitant Therapy of 
Special Interest eCRF.
Treatment with concomitant therapies for other medical conditions such as diabetes and 
hypertension is permitted during the study.
7.7.3. Rescue Therapy
No rescue therapy options are available during the study.  Patients are allowed to use low-
potency TCS as background therapy for comfort if needed. Patients who experience worsening 
and unacceptable symptoms of AD should consider discontinuing from the study.  Patients 
requiring more than low-potency TCS to manage their symptoms should also be discontinued.

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Hydrocortisone 2.5% ointment will be supplied by the sponsor for use during the first 2 years of 
the treatment period (dispensed at Visits 1-10 only).  In the event that providing this topical 
formulation during the first 2 years is not possible, an alternate, equivalent potency TCS cream 
and/or ointment may be provided by the sponsor.  Use of sponsor-supplied TCS should be 
recorded via weight of returned tubes as indicated in the Schedule of Activities (Section 2).  
Sponsor will not provide or reimburse the cost of TCS at Visit 11 or after.
In the event that the sponsor is unable to supply TCS during the first 2 years of the treatment 
period, commercially available hydrocortisone 2.5% ointment or an equivalent-potency TCS 
cream and/or ointment that is in line with local practices can be supplied by the sponsor or the 
sites. Refer to Appendix 7 for guidance on potency equivalence.  
On the days of study visits, topical therapy should not be applied before the patient has 
undergone all study procedures and clinical evaluations to allow adequate assessment of skin 
dryness.
7.8.
Treatment after the End of the Study
7.8.1. Continued Access
After the conclusion of the study, continued access to baricitinib will not be provided to patients.  
Patients will be referred to their local treatment centers for AD therapy as clinically indicated.

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Temporary Interruption from 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.  
For example, investigational product should be temporarily interrupted if the patient experiences
a cardiovascular AE considered to be related to study treatment, is graded as moderate (Grade 2
according to Common Terminology Criteria for Adverse Events [CTCAE] Version 3.0), and that 
does not resolve promptly with supportive care.  Except in cases of emergency, it is 
recommended that the investigator consult with Lilly (or its designee) before temporarily 
interrupting therapy for reasons other than those defined in Table JAIX.4.  
Patients who met criteria for temporary interruption of investigational product during the 
originating study or during screening may be enrolled in Study JAIX, but will remain on 
temporary interruption until the criteria for resuming investigational product has been met.
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table JAIX.4, specific guidance is provided for temporarily interrupting treatment and 
determining when treatment may be restarted. Retest frequency and timing of follow-up 
laboratory tests to monitor the abnormal finding is at the discretion of the investigator.  
Investigational product that was temporarily interrupted because of an AE or abnormal 
laboratory value not specifically covered in Table JAIX.4 may be restarted at the discretion of 
the investigator.

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8.1.2. Permanent Discontinuation from Investigational Product
Investigational product should be permanently discontinued if the patient requests to discontinue 
investigational product.
Discontinuation of the investigational product for abnormal liver tests should be considered by 
the investigator when a patient meets 1 of the following conditions after consultation with the 
Lilly-designated medical monitor:

ALT or AST >8 x upper limit of normal (ULN)

ALT or AST >5 x ULN for >2 weeks

ALT or AST >3 x ULN and total bilirubin level (TBL) >2 x ULN or 
international normalized ratio >1.5

ALT or AST >3 x ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, and/or rash

alkaline phosphatase (ALP) >3 x ULN

ALP >2.5 x ULN and TBL >2 x ULN

ALP >2.5 x ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, and/or rash
Note:  Patients who are discontinued from investigational product because of a 
hepatic event or liver test abnormality should have additional hepatic safety data 
collected via the hepatic safety eCRF.
Investigational product should be permanently discontinued if any of the following laboratory 
abnormalities are observed:

white blood cell count <1000 cells/µL (1.00 × 103/µL or 1.00 GI/L)

absolute neutrophil count <500 cells/µL (0.50 × 103/µL or 0.50 GI/L)

lymphocyte count <200 cells/µL (0.20 × 103/µL or 0.20 GI/L)

hemoglobin <6.5 g/dL (<65.0 g/L)
Note:  Temporary interruption rules (see Section 8.1.1) must be followed where 
applicable.  For laboratory values that meet permanent discontinuation thresholds, 
investigational product should be discontinued.  However, if in the opinion of the 
investigator the laboratory abnormality is due to intercurrent illness such as 
cholelithiasis or another identified factor, laboratory tests may be repeated.  Only 
when the laboratory value meets resumption thresholds (Table JAIX.4) following the 
resolution of the intercurrent illness or other identified factor, may the investigator 
restart investigational product, after consultation with the Lilly-designated medical 
monitor.

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In addition, patients will be discontinued from investigational product in the following 
circumstances:

pregnancy

malignancy (except for successfully treated basal or squamous cell skin 
carcinoma)

HBV DNA is detected with a value above limit of quantitation or 2 sequential 
tests return a value below the limit of quantitation (see Section 9.4.6)

certain prohibited medications are taken per Section 7.7.1

develop a VTE 
Note:  Patients who develop a VTE may have additional follow up and testing 
recommended (see Section 9.4.8. and Appendix 6).
If a patient develops multiple risk factors for a VTE during the conduct of the study, the 
investigator may consider study discontinuation if he/she believes the risk outweighs the benefits 
of continuing therapy.  It is recommended that the investigator consult with Lilly (or its 
designee) before discontinuing therapy for this reason.  
Patients discontinuing from the investigational product prematurely for any reason should 
complete AE and other follow-up procedures per Section 2 (Schedule of Activities), Section 9.2
(Adverse Events), and Section 9.4 (Safety) of this protocol.
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 clinical research physician agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
sponsor clinical research physician 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 may choose to withdraw from the study for any reason at any time, and the reason for 
early withdrawal will be documented.
Some possible reasons that may lead to permanent discontinuation include the following:

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

study termination may occur in a specific country or region when baricitinib is approved 
for the treatment of AD and becomes reimbursed or commercially available in that 
country or region, or a negative regulatory opinion is received in that country or region

investigator decision
o
The investigator decides that the patient should be discontinued from the 
study.
o
If the patient, for any reason, requires treatment with another therapeutic 
agent (not allowed as part of rescue therapy [Section 7.7.3]) that has been 
demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new 
agent.

patient 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 per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol.
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 and Appendix 4 list the laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Primary Efficacy Assessments
Eczema Area and Severity Index Scores (EASI): The EASI assesses extent of disease at 4 
body regions and measures 4 clinical signs: (1) erythema, (2) induration/papulation, (3) 
excoriation, and (4) lichenification, each on a scale of 0 to 3. The EASI confers a maximum 
score of 72. The EASI evaluates 2 dimensions of AD: disease extent and clinical signs (Hanifin
et al. 2001).  
9.1.2. Secondary Efficacy Assessments
9.1.2.1.
Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-
AD)
The IGA used in this study, the vIGA-AD (referred to as the IGA throughout the protocol) 
measures the IGA of the patient’s overall severity of their AD, based on a static, numeric 5-point 
scale from 0 (clear skin) to 4 (severe disease).  The score is based on an overall assessment of the 
degree of erythema, papulation/induration, oozing/crusting, and lichenification.
9.1.2.2.
Eczema Area and Severity Index scores
The EASI assesses extent of disease at 4 body regions and measures 4 clinical signs: 
(1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale 
of 0 to 3. The EASI confers a maximum score of 72. The EASI evaluates 2 dimensions of AD: 
disease extent and clinical signs (Hanifin et al. 2001).  
BSA affected by AD will be derived from data collected as part of the EASI assessment.
9.1.2.3.
SCORing Atopic Dermatitis
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical 
characteristics to determine disease severity: (1) erythema, (2) edema/papulation, 
(3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness. The SCORAD index also 
assesses subjective symptoms of pruritus and sleep loss. These 3 aspects (extent of disease, 
disease severity, and subjective symptoms) combine to give a maximum possible score of 103
(Stalder et al. 1993; Kunz et al. 1997; Schram et al. 2012).

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9.1.2.4.
Hospital Anxiety Depression Scale
The Hospital Anxiety Depression Scale (HADS) is a 14-item self-assessment scale that 
determines the levels of anxiety and depression that a patient is experiencing over the past week.
The HADS utilizes a 4-point Likert scale (for example, 0 to 3) for each question and is intended 
for ages 12 to 65 years (Zigmond and Snaith 1983; White et al. 1999).  Scores for each domain 
(anxiety and depression) can range from 0 to 21, with higher scores indicating greater anxiety or 
depression (Zigmond and Snaith 1983; Snaith 2003).
9.1.3. Health Outcomes and Quality-of-Life Measures
The patient self-reported questionnaires will be administered via either an electronic patient diary 
or via an electronic tablet.  Questionnaires will have been translated into the native language of 
the country and/or region and linguistically validated.
9.1.3.1.
Patient-Oriented Eczema Measure
The POEM is a simple, 7-item, patient-administered scale that assesses disease severity in 
children and adults.  Patients respond to questions about the frequency of 7 symptoms (itching, 
sleep disturbance, bleeding, weeping/oozing, cracking, flaking, and dryness/roughness) over the 
last week.  Response categories include “No days,” “1-2 days,” “3-4 days,” “5-6 days,” and 
“Every day” with corresponding scores of 0, 1, 2, 3, and 4, respectively.  Scores range from 0-28 
with higher total scores indicating greater disease severity (Charman et al. 2004).
9.1.3.2.
Itch Numeric Rating Scale
The Itch NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 
representing “no itch” and 10 representing “worst itch imaginable.”  Overall severity of a 
patient’s itching is indicated by selecting the number that best describes the worst level of itching 
in the past 24 hours (Naegeli et al. 2015; Kimball et al. 2016).
9.1.3.3.
Atopic Dermatitis Sleep Scale
The Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, patient-administered questionnaire 
developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of 
waking, and difficulty getting back to sleep the previous night.  Patient’s rate their difficulty 
falling asleep and difficulty getting back to sleep, items 1 and 3, respectively, using a 5-point 
Likert-type scale with response options ranging from 0 “not at all” to 4 “very difficult.”  Patients 
report their frequency of waking the previous night, item 2, by selecting the number of times 
they woke up each night, ranging from 0 to 29 times.  The ADSS is designed to be completed 
each day with respondents thinking about sleep “last night.” Each item is scored individually.  
9.1.3.4.
Skin Pain Numeric Rating Scale
Skin Pain NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 
0 representing “no pain” and 10 representing “worst pain imaginable.” Overall severity of a 
patient’s skin pain is indicated by selecting the number that best describes the worst level of skin 
pain in the previous 24 hours.

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9.1.3.5.
Patient Global Impression of Severity
The Patient Global Impression of Severity–Atopic Dermatitis (PGI-S-AD) is a single-item 
question asking the patient how they would rate their overall AD symptoms over the past 
24 hours.  The 5 categories of responses range from “no symptoms” to “severe.”
9.1.3.6.
Dermatology Life Quality Index
The DLQI is a simple, patient-administered, 10-item, validated, quality-of-life questionnaire that 
covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, 
personal relationships, and treatment. The recall period of this scale is over the “last week.” 
Response categories include “not at all,” “a little,” “a lot,” and “very much,” with corresponding 
scores of 0, 1, 2, and 3, respectively, and unanswered (“not relevant”) responses scored as 0 as 
applicable. Scores range from 0-30 with higher scores indicating greater impairment of quality 
of life. A DLQI total score of 0 to 1 is considered as having no effect on a patient’s 
health-related quality of life (Hongbo et al. 2005), and a 4-point change from baseline is 
considered as the minimal clinically important difference threshold (Khilji et al. 2002; Basra
et al. 2015).
9.1.3.7.
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 that provides 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 or her current health state using a 0 to 100 mm Visual Analog Scale 
(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 checking (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 essentially attaches values (also called weights) to each of the levels in each 
dimension (Herdman et al. 2011; EuroQol Group 2015 [WWW]).
9.1.3.8.
Work Productivity and Activity Impairment Questionnaire–Atopic 
Dermatitis
The Work Productivity and Activity Impairment Questionnaire–Atopic Dermatitis (WPAI-AD) 
records impairment due to AD during the past 7 days.  The WPAI-AD 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.

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9.1.4. Appropriateness of Assessments
All assessments utilized in this study are standard, widely used, and generally recognized as 
reliable, accurate, and relevant except ADSS and Skin Pain NRS, which are currently being 
developed and validated according to regulatory guidances.
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of 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 their assessment of the 
potential relatedness of each AE to 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.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in 1 of the following outcomes:

death

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
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 1 of the other outcomes listed in the definition above.  Examples of 
such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.
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 as per 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 sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.  Patients with a serious hepatic AE should have additional data collected using the 
hepatic safety 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 summary 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 recording 
and expedited reporting of SUSARs that are consistent with global regulations and the associated 
detailed guidances.

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9.2.2. Adverse Events of Special Interest
AEs of special interest will include the following:

infections (including tuberculosis, herpes zoster, or opportunistic infections)

malignancies

hepatic events (see Section 9.4.7)

major adverse cardiovascular events (MACE) (see Section 9.4.9)

thrombotic events (such as deep vein thrombosis and pulmonary embolism) (see 
Section 9.4.8).
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 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 should be measured according to the Schedule of Activities 
(Section 2).
9.4.2. Physical Exam
For each patient, a symptom-directed physical examination will be performed at all visits.  
A complete physical examination may be performed at the investigator’s discretion at any time a 
patient presents with physical complaints.
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). Lilly or its designee will provide the investigator with the 

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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 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 and the SAE and/or AE leading to discontinuation should be 
included on the AE form, and the process for reporting SAEs should be followed.
9.4.5. Self-Harm and Follow-Up Supplement Forms
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the self-harm follow-up form.  The self-harm 
follow-up form is a series of questions that provides a more detailed description of the behavior 
cases.
9.4.6. Hepatitis B Virus DNA Monitoring
Hepatitis B virus DNA testing will be performed in enrolled patients who tested positive for anti-
hepatitis B core antibody (HBcAb) at screening in the originating study (Study JAIW).
Patients who are HBcAb positive and HBV DNA negative (undetectable) at screening (Visit 1) 
in the originating study (Study JAIW) will require measurement of HBV DNA per Schedule of 
Activities (Section 2), regardless of their hepatitis B surface antibody (HBsAb) 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 will resume as specified in the Schedule of 
Activities (Section 2).

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
If the patient has 2 or more test results with a value “below limit of quantitation”
or a test result above the limit of quantitation, the patient will be permanently 
discontinued from investigational product (see Section 8.1.2) and should be 
referred to a hepatology specialist.  
9.4.7. Hepatic Safety Monitoring and Data Collection
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 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.
Criteria for discontinuation of investigational products (either temporary interruption or 
permanent discontinuation) due to abnormal ALT, AST, TBL, or ALP are detailed in 
Section 8.1.
Additional safety data should be collected via the hepatic 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 because of a hepatic event or abnormality of 
liver tests

hepatic event considered to be an SAE
See Appendix 4 and Appendix 5 for a description of hepatic laboratory values that warrant 
exclusion from the study, temporary or permanent discontinuation of investigational product, or 
additional safety collection via the hepatic eCRF.
9.4.8. VTE Assessment
If a patient develops the signs and symptoms of a deep vein thrombosis or pulmonary embolism, 
appropriate local laboratory tests and imaging should be performed, as necessary, for diagnosis 
of the event.  For confirmed cases, additional laboratory testing should be performed as outlined 
in Appendix 6.  All suspected VTE events will be independently adjudicated by a Clinical Event
Committee (see Section 10.3.6.1).
9.4.9. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.

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The Lilly clinical research physician will monitor safety data throughout the course of the study. 
Lilly will review SAEs within time frames mandated by company procedures. The Lilly clinical 
research physician will, as is appropriate, consult with the functionally independent Global 
Patient Safety 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 designee) may require further evaluation.
All deaths and SAE reports will be reviewed by Lilly during the clinical trial. 
Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular and VTEs. AE 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, MI, stroke), other cardiovascular events 
(such as hospitalization for unstable angina, hospitalization for heart failure, 
serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary 
revascularization such as coronary artery bypass graft or percutaneous coronary 
intervention), VTEs 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.
9.5.
Pharmacokinetics
Not applicable.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenetics
Not applicable. 
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics, 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 DNA, RNA, 
proteins, lipids, and other cellular elements.
Blood samples for nonpharmacogenetic 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 AD, mechanism of action of baricitinib, and/or research 
method or in validating diagnostic tools or assay(s) related to AD.

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All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if local regulations and ethical review boards (ERBs) impose shorter time 
limits, at a facility selected by Lilly.  This retention period enables use of new technologies, 
response to regulatory questions, and investigation of variable response that may not be observed 
until later in the development of baricitinib or after baricitinib becomes commercially available.
9.9.
Medical Resource Utilization and Health Economics
Health Economics will be evaluated in this study utilizing the EQ-5D-5L and WPAI-AD (see 
Section 9.1.3).  Medical Resource Utilization parameters will not be evaluated in this study.

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10. Statistical Considerations
10.1. Sample Size Determination
The study is descriptive in nature and the sample size is not based on any statistical power 
calculations.  All of the approximate 450 patients participating in the originating study can be 
assessed for eligibility to participate in Study JAIX.
10.2. Populations for Analyses
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on all 
enrolled patients who receive at least 1 dose of investigational product in Study JAIX, even if the 
patient does not follow the protocol.  Significant protocol violations will be described in the 
SAP.
Unless otherwise specified, safety analyses will be performed on all enrolled patients who 
receive at least 1 dose of investigational product and who do not discontinue from the study for 
the reason “Lost to Follow-up” at the first postbaseline visit. Further details of other populations 
will be described in the SAP. 
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
As this study is open-label and all patients are receiving baricitinib 2-mg, no hypothesis testing 
will be performed.  Data will be summarized both overall and by prior-treatment-received in 
Study JAIW. Data from this trial may be integrated with other trials.
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.
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 (CSR).  Additional exploratory analyses of the data will be conducted 
as deemed appropriate.
All discrete efficacy variables will be summarized using frequencies and percentages.  
Continuous efficacy and health outcome variables will be summarized using number of patients, 
mean, standard deviation, median, minimum, and maximum.
The methods used to handle missing data will be specified in the SAP.
Frequencies and percentages will be computed for AEs, discontinuation, and other categorical 
safety data. 
All patients who discontinue the study or the study treatment at any time for any reason will be 
defined as nonresponders for the NRI summary of categorical efficacy variables such as IGA 0/1 
or EASI 50/75/90 after discontinuation and onward.  

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10.3.2. Descriptive Population Analyses
10.3.2.1. Patient Disposition
All patients who discontinue from the study or the study treatment will be identified, along with 
their reason for discontinuation. Reasons for discontinuation from the study will be summarized. 
Additional summary may be produced by prior treatment received.
10.3.2.2. Patient Characteristics
Descriptive statistics for continuous variables will be produced including number of patients, 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized using frequencies and percentages.
10.3.2.3. Concomitant Therapy
Concomitant medications will be descriptively summarized in terms of frequencies and 
percentages using the safety population. Additional summary may be produced by prior 
treatment received.  The medications will be coded accordingly.
10.3.2.4. Treatment Compliance
Treatment compliance with study medication will be evaluated at every clinic visit through the 
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, unless 
the patient’s investigational product is withheld by the investigator for safety reasons; 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, that is, compliance ≥120%.
10.3.3. Efficacy Analyses
Categorical efficacy variables will be summarized in terms of frequencies and percentages.  
Nonresponder imputation will be used as described in Section 10.3.1. Continuous efficacy 
variables will be descriptively summarized in terms of number of patients, mean, standard 
deviation, median, minimum, and maximum.  

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10.3.4. Safety Analyses
All safety data will be summarized overall and by prior therapy received using the safety 
population. 
Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred or worsened 
in severity after the first dose of study treatment. The number of TEAEs as well as the number 
and percentage of patients who experienced at least 1 TEAE will be summarized using Medical 
Dictionary for Regulatory Activities (MedDRA) for each system organ class (or a body system) 
and each preferred term. Serious adverse events and AEs that lead to discontinuation of 
investigational product will also be summarized. 
Categorical variables, including the incidence of AEs of special interest, together with individual 
analyses of clinical laboratory results and vital signs are not planned for this Study, but will be 
included in an integrated database.
Further summaries may be performed and will be planned in the SAP.
Data collected after initiation of rescue therapy will be summarized as appropriate.
10.3.5. Other Analyses
10.3.5.1. Health Outcome Measures
The health outcome measures will be summarized using methods described for continuous or
categorical data as described for efficacy measures in Section 10.3.3.
10.3.6. Interim Analyses
10.3.6.1. Adjudication Committee
A Clinical Event Committee will adjudicate potential MACE (cardiovascular death, MI, stroke), 
other cardiovascular events (such as hospitalization for unstable angina, hospitalization for heart 
failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary 
revascularization such as coronary artery bypass graft or percutaneous coronary intervention), 
VTEs, and noncardiovascular deaths.  Details of membership, operations, recommendations from 
the Committee, and the communication plan will be documented in the Charter.

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Bieber, T. Atopic dermatitis. Ann Dermatol. 2010;22(2):125-137.
Bieber T, Straeter B. Off-label prescriptions for atopic dermatitis in Europe. Allergy. 
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Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and 
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Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors 
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Herdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, Bonsel G, Badia X.
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of life into practice: What do dermatology life quality index scores mean? J Invest Dermatol. 
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Khilji FA, Gonzalez M, Finlay AY. Clinical meaning of change in Dermatology Life Quality 
Index scores. Br J Dermatol. 2002;147(suppl 62):25-54.
Kimball AB, Naegeli AN, Edson-Heredia E, Lin CY, Gaich C, Nikai E, Yosipovitch G. 
Psychometric properties of the Itch Numeric Rating Scale in patients with moderate-to-severe 
plaque psoriasis. Br J Dermatol. 2016;175(1):157-162.
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population. Pediatrics. 2008;122(4):812-824.
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the SCORAD Index: consensus report of the European Task Force on Atopic Dermatitis. 
Dermatology. 1997;195(1):10-19. 
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care of atopic eczema in Germany: results of the national health care study AtopicHealth.
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ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic 
stromal lymphopoietin. Proc Natl Acad Sci U S A. 2005;102(41):14795-14800.
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Naegeli AN, Flood E, Tucker J, Devlen J, Edson-Heredia E. The Worst Itch Numeric Rating 
Scale for patients with moderate to severe plaque psoriasis or psoriatic arthritis. Int J 
Dermatol. 2015;54(6):715-722.
Nomura T, Kabashima K. Advances in atopic dermatitis in 2015. J Allergy Clin Immunol. 
2016;138(6):1548-1555.
Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, Goudie DR, 
Sandilands A, Campbell LE, Smith FJ, O’Regan GM, Watson RM, Cecil JE, Bale SJ, 
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Munro CS, El Houate B, McElreavey K, Halkjaer LB, Bisgaard H, Mukhopadhyay S, 
McLean WH. Common loss-of-function variants of the epidermal barrier protein filaggrin are 
a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441-446.
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Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
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SCORAD and POEM for atopic eczema: responsiveness and minimal clinically important 
difference. Allergy. 2012;67(1):99-106.
Simpson EL. Comorbidity in atopic dermatitis. Curr Dermatol Rep. 2012;1(1):29-38.
Snaith RP. The Hospital Anxiety and Depression Scale. Health Qual Life Outcomes. 2003;1:29.
Stalder J, Taïeb A. Severity scoring of atopic dermatitis: the SCORAD index. Consensus report 
of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31.
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Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, del Carmen Morales L, Gonzaga JR, 
Yakushin S, Ishii T, Emoto K, Beattie S, Arora V, Gaich CL, Rooney T, Schlichting D, 
Macias WL, de Bono S, Tanaka Y. Baricitinib versus placebo or adalimumab in rheumatoid 
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TE, Duffin KL, Haas JV, Macias WL, Janes JM. Baricitinib in diabetic kidney disease: Results 
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Vaddi K, Luchi M. JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral 
DMARD therapy. Expert Opin Investig Drugs. 2012;21(7):961-973.
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Depression Scale for use with adolescents. Br J Psychiatry. 1999;175(5):452-454.
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Bautista DM. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to 
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on sleep quality in Japanese patients with atopic dermatitis. J Dermatol Sci. 2013;72(2):195-
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1983;67(6):361-370.

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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
AD
atopic dermatitis
ADSS
Atopic Dermatitis Sleep Scale
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.
ALT
alanine aminotransferase
ALP
alkaline phosphatase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
BCG
Bacillus Calmette Guérin
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
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.
BSA
body surface area
CI
confidence interval
C-SSRS
Columbia Suicide Severity Rating Scale
CSR
clinical study report
DLQI
Dermatology Life Quality Index
EASI
Eczema Area and Severity Index
EASI50
50% improvement from baseline in EASI
EASI75
75% improvement from baseline in EASI
eCOA
electronic clinical outcome assessment

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eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the trial are 
those who have been assigned to a treatment.
Enter
Patients entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
ePRO
electronic patient-reported outcomes
EQ-5D-5L
European Quality of Life–5 Dimensions–5 Levels
ERB
ethical review board
ETV
early termination visit
GCP
good clinical practice
HADS
Hospital Anxiety Depression Scale
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBV
hepatitis B virus
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IGA
Investigator’s Global Assessment
IL
interleukin
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
INR
international normalized ratio
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.
IWRS
interactive web-response system
JAK
Janus kinase
LSM
least squares mean

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MACE
major adverse cardiovascular events
MI
myocardial infarction
MMRM
mixed-effects model of repeated measures
NRI
nonresponder imputation
NRS
Numeric Rating Scale
PDE-4
phosphodiesterase type 4
POEM
Patient-Oriented Eczema Measure
QD
once daily
RA
rheumatoid arthritis
SAE
serious adverse event
SAP
statistical analysis plan
SCORAD
SCORing Atopic Dermatitis
SUSAR
suspected unexpected serious adverse reaction
TBL
total bilirubin level
TCNI
topical calcineurin inhibitor
TCS
topical corticosteroids
TEAE
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, which does not necessarily have to have a causal relationship 
with this treatment.
TSLP
thymic stromal lymphopoietin
TYK2
tyrosine kinase 2
VAS
Visual Analog Scale
vIGA-AD
validated Investigator’s Global Assessment for Atopic Dermatitis
VTE
venous thromboembolic event
WPAI-AD
The Work Productivity and Activity Impairment–Atopic Dermatitis

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Appendix 2.
Clinical Laboratory Tests
Hematology
a,b
Clinical Chemistry
a,b
Hemoglobin
Serum concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Absolute reticulocyte count
Total bilirubin
Mean cell volume
Direct bilirubin
Mean cell hemoglobin
Alkaline phosphatase
Mean cell hemoglobin concentration
Alanine aminotransferase (ALT)
Leukocytes (WBC)
Aspartate aminotransferase (AST)
Platelets
Blood urea nitrogen (BUN)
Creatinine
Absolute counts of:
Cystatin C
Neutrophils, segmented
Uric acid
Neutrophils, juvenile (bands)
Calcium
Lymphocytes
Glucose
Monocytes
Albumin
Eosinophils
Total protein
Basophils
Estimated glomerular filtration rate (eGFR)d
Creatine phosphokinase (CPK)
Urinalysis
a,b,c
Color
Lipidsa,e
Specific gravity
Total cholesterol
pH
Low-density lipoprotein
Protein
High-density lipoprotein
Glucose
Triglycerides
Ketones
Bilirubin
Other Testsa
Urobilinogen
HBV DNA
f
Blood
Exploratory storage samples (serum, plasma and mRNA)
Leukocyte esterase
Pregnancy testg
Nitrite
Serum immunoglobulin (IgE)
Abbreviations:  HBcAb+ = hepatitis B core antibody positive; HBV = hepatitis B virus; RBC = red blood cell; WBC 
= white blood cell.
a Assayed by sponsor-designated laboratory.
b Unscheduled or repeat blood chemistry, hematology, and urinalysis panels may be performed at the discretion of 
the investigator, as needed.
c Microscopic examination of sediment performed only if abnormalities are noted on the routine urinalysis.
d eGFR for serum creatinine calculated by the central laboratory using the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) Creatinine 2009 equation.
e Fasting lipid profile. 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.
f HBV DNA testing will be done in those patients who are HBcAb+ at screening of originating study, Study JAIW.
g For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at all specified 
visits.  If required per local regulations and/or institutional guidelines, pregnancy testing can occur at other times 
during the study treatment period.

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Appendix 3.
Study Governance Considerations
Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1.
Informed Consent
The investigator is responsible for ensuring the following:

that the patient understands the potential risks and benefits of participating in 
the study.

that informed consent is given by each patient.  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 trial.
Appendix 3.1.2.
Ethical Review
The investigator 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 Eli Lilly and 
Company (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 current investigator brochure (IB) and updates during the course of the 
study

ICF

relevant curricula vitae.
Appendix 3.1.3.
Regulatory Considerations
This study will be conducted in accordance with:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences (CIOMS) International Ethical Guidelines

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
applicable ICH GCP Guidelines

applicable laws and regulations.
Some of the obligations of the sponsor will be assigned to a third party.
Appendix 3.1.4.
Investigator Information
Physicians with a specialty in dermatology will participate as investigators in this clinical trial.
Appendix 3.1.5.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.6.
Final Report Signature
Lilly will select a qualified investigator(s) from among investigators participating in the design, 
conduct, and/or analysis of the study to serve as the clinical study report (CSR) coordinating 
investigator.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the CSR coordinating investigator.
The 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

provide 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

review and evaluate CRF data and use standard computer edits to detect errors in 
data collection

conduct a quality review of the database.

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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 will be encoded and stored in InForm.  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 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, the investigator, or the ERB of the study 
site judges it necessary for medical, safety, regulatory, or other reasons consistent with 
applicable laws, regulations, and GCP.
Appendix 3.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP.

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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, its designee, or the 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 cell; WBC = white blood cell.
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.
Liver Function Testing and Hepatic Safety 
Monitoring
Liver Function Testing and Hepatic Safety Monitoring
Analyte
Exclusion
Criteria
Additional 
Hepatic 
Testing
Hepatic eCRF 
Reporting
Temporary 
Interruption of 
IP
Permanent Discontinuation 
of IP after Consultation 
with the Lilly-Designated 
Medical Monitor
Protocol 
Section
Section 6.2
Section 9.4.7
Section 9.4.7
Section 8.1.1
Section 8.1.2
ALT/AST
≥2 x ULN
ALT only
≥3 x ULN
ALT only
≥5 x ULN on ≥2 
consecutive tests
≥5 x ULN

>8 x ULN

>5 x ULN for 
>2 weeks

>3 x ULN AND TBL 
>2 x ULN or INR >1.5

>3 x ULN with 
symptomsa
ALP
≥2 x ULN
≥2 x ULN
≥2 x ULN on ≥2 
consecutive tests
No applicable 
criteria

>3 x ULN

>2.5 x ULN AND TBL 
>2 x ULN 

>2.5 x ULN with 
symptomsa
TBL
≥1.5 x ULN
≥2 x ULN
≥2 x ULN
(excluding 
Gilbert’s 
syndrome)
No applicable 
criteria

ALT or AST >3 x ULN 
AND TBL >2 x ULN

ALP >2.5 x ULN AND 
TBL >2 x ULN
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
INR = international normalized ratio; IP = investigational product; TBL = total bilirubin level; ULN = upper 
level of normal.
a
Fatigue, nausea, vomiting, right upper-quadrant pain or tenderness, fever, and/or rash.

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Appendix 6.
Monitoring Tests for Confirmed VTE
Selected tests may be obtained in the event of a confirmed venous thromboembolic event (VTE)
and may be required in follow-up with patients in consultation with Eli Lilly and Company, its 
designee, or the clinical research physician.  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 7.
Classification of Potency for Topical 
Corticosteroids
Potency
Class
Topical Corticosteroid
Formulation
Ultra high
I
Clobetasol propionate
Cream 0.05%
Diflorasone diacetate
Ointment 0.05%
High
II
Amcinonide
Ointment 0.1%
Betamethasone dipropionate
Ointment 0.05%
Desoximetasone
Cream or ointment 0.025%
Fluocinonide
Cream, ointment or gel 0.05%
Halcinonide
Cream 0.1%
III
Betamethasone dipropionate
Cream 0.05%
Betamethasone valerate
Ointment 0.1%
Diflorasone diacetate
Cream 0.05%
Triamcinolone acetonide
Ointment 0.1%
Moderate
IV
Desoximetasone
Cream 0.05%
Fluocinolone acetonide
Ointment 0.025%
Fludroxycortide
Ointment 0.05%
Hydrocortisone valerate
Ointment 0.2%
Triamcinolone acetonide
Cream 0.1%
V
Betamethasone dipropionate
Lotion 0.02%
Betamethasone valerate
Cream 0.1%
Fluocinolone acetonide
Cream 0.025%
Fludroxycortide
Cream 0.05%
Hydrocortisone butyrate
Cream 0.1%
Hydrocortisone valerate
Cream 0.2%
Triamcinolone acetonide
Lotion 0.1%
Low
VI
Betamethasone valerate
Lotion 0.05%
Desonide
Cream 0.05%
Fluocinolone acetonide
Solution 0.01%
VII
Dexamethasone sodium phosphate
Cream 0.1%
Hydrocortisone 
Lotion, cream, or ointment 2.5%
Hydrocortisone acetate
Cream 1%
Methylprednisolone acetate
Cream 0.25%
Source: WHO (1997) and Tadicherla et al. 2009.

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Appendix 8.
Investigator Global Assessment

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Appendix 9.
Protocol   I4V MC JAIX(c) Summary - A 
Multicenter, Open-Label, Phase 3 Study to Evaluate 
the Efficacy and Safety of Baricitinib in Adult Patients 
with Moderate to Severe Atopic Dermatitis
Overview
Protocol I4V-MC-JAIX, A Multicenter, Open-Label, Phase 3 Study to Evaluate the Efficacy and 
Safety of Baricitinib in Adult Patients with Moderate to Severe Atopic Dermatitis, has been 
amended.  The new protocol is indicated by amendment (c) and will be used to conduct the study 
in place of any preceding version of the protocol.
There are 3 main changes in this protocol amendment:
1. Study duration extended for all participating patients
2. Study design updated to allow patients who complete Study JAIW to subsequently enter 
Study JAIX
3. Primary efficacy endpoint changed.
Amendment Summary for Protocol I4V-MC-JAIX Amendment (c)
Section # 
Description of Change
Brief Rationale
Section 1,4 and 5
Primary efficacy endpoint was changed.
Updated language to reflect the change in 
eligibility criteria that will allow responders 
who completed Study JAIW through Week 104 
to be enrolled.
Objectives were updated to clarify that 
analyses will consider treatment received and 
responder status.
Exploratory objectives/endpoints were updated 
to reflect the fact that changes in IgE and 
To reflect the change made in the 
originating study, Study JAIW, where the 
primary endpoint was changed from IGA 
0,1 to EASI75.
To allow all patients participating in Study 
JAIW the opportunity to receive IP (2-mg 
QD), the study design has been updated to 
allow “responders” from Study JAIW to 
enter this study (Study JAIX) after 
completing the full treatment period of that 
study.
The change was made to align with the 
study design change which now allows 
inclusion of Study JAIW responders.  Data 
for these patients may be analyzed 
separately from the data for nonresponders 
and partial responders.
Specific analysis of changes in IgE and 
eosinophil levels are not currently planned 

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Section # 
Description of Change
Brief Rationale
eosinophil levels will not be considered.  
to be considered as exploratory 
objectives/endpoints.
Section 1
Extended treatment duration by approximately 
2 years.
The treatment period was extended to allow 
for continued efficacy and safety data 
collection as well as to allow patients to 
continue to receive baricitinib treatment for 
up to another 2 years.
Section 2, Table
JAIX.1. Schedule 
of Activities
Added scheduled study visits every 4 months 
to the end of the study treatment period for a 
total of 6 new visits (Visits 12 through 17)
during the 2-year extension.
Treatment visits were added at a frequency 
of every 4-months to allow for appropriate 
ongoing safety monitoring during the study.
Section 5 and 
Figure JAIX 1
Updated to reflect the 2-year treatment 
extension and associated visit schedule.
Figure was updated to include the additional 
visits.
As described above, the treatment period 
was extended to allow for continued 
efficacy and safety data collection as well 
as to allow patients to continue to receive 
baricitinib treatment for up to another 2 
years.
Section 1, 3.2, 5.1, 
5.2, 5.4, 6 and 
10.1
Updated the number of patients that may be 
enrolled.
Updated language to reflect the change in 
eligibility criteria that will allow responders 
who completed Study JAIW through Week 104
to be enrolled.
The study design has been updated to allow 
“responders” from Study JAIW to enter this 
study (Study JAIX) after completing the 
full treatment period of that study. This 
change, in effect, makes all patients 
enrolled in Study JAIW eligible for 
assessment to enter Study JAIX at some 
point at or after JAIW Visit 8.  The 
approximate sample size in Study JAIW is 
450 patients.   
To allow all patients participating in Study 
JAIW the opportunity to receive IP (2-mg 
QD), the study design has been updated to 
allow “responders” from Study JAIW to 
enter this study (Study JAIX) after 
completing the full treatment period of that 
study.
Section 5.1.1
Added text that will allow Study JAIW 
“responders” to take a voluntary drug 
interruption between Study JAIW Visit 15 and 
Study JAIX Visit 1.
Some patients who have achieved and 
maintained treatment response in Study 
JAIW may be receiving placebo or 1-mg 
baricitinib QD.  This voluntary interruption 
will give patients and investigators time to 
see if the patients’ condition changes after 
stopping treatment which may inform their 
decision to enter into Study JAIX.
Section 6.1
Eligibility criteria were updated to include 
responders who completed Study JAIW 
through Week 104.
To allow all patients participating in Study 
JAIW the opportunity to receive IP (2-mg 
QD), the study design has been updated to 
allow “responders” from Study JAIW to 
enter this study (Study JAIX) after 

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Section # 
Description of Change
Brief Rationale
completing the full treatment period of that 
study.
Section 7.6
Treatment period was updated.
Section was updated to reflect the extension
of the treatment period for the reasons 
described above.  There is no change to 
how treatment compliance is assessed nor 
what is considered significant 
noncompliance. 
Section 7.7.3
Updated language to reflect that TCS will not 
be provided or reimbursed by the sponsor for 
visit 11 and after (i.e., dispensed at Visits 1-10 
only).
The purpose for this extension is to allow 
patients the opportunity to continue to 
receive baricitinib while allowing clinicians 
and patients freedom to use a low potency 
TCS product/dosing form (e.g., cream, 
ointment) that is preferred and is available 
as part of local standard of care.
Section 8.2
Added that study termination may occur based 
on regulatory disapproval, or approval and 
reimbursement and commercial availability of 
baricitinib for the treatment of AD, in a 
country or region.
Early termination of the study in a 
country/region as a result of a favorable or 
unfavorable regulatory opinion will allow 
patients to receive treatment that is in line 
with what the local or regional regulatory 
agency consider appropriate standard of 
care. 
Section 9.1.1 and
9.1.2
Updated efficacy assessment descriptions and 
section heading numbering.
To reflect the change made in the 
originating study, Study JAIW, where the 
primary endpoint was changed from IGA 
0,1 to EASI75.
Section 10.3.1 and 
10.3.4
Updated safety analyses description.
Safety endpoints are better assessed in the 
context of combining the safety data from 
the originating study with the safety data 
from an extension study. Therefore, some 
of the planned safety analyses (e.g., clinical 
laboratory analysis, vital signs, and AEs of 
special interest) will now be conducted as 
part of the integrated safety database and 
not at the study level. 

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
1. Synopsis
Objectives/Endpoints:
Objectives
Endpoints
Primary
To describe the clinical response to baricitinib 2-mg 
QD in patients with moderate to severe AD by prior 
treatment received (ie., baricitinib 2-mg, 1-mg, or 
placebo) received and responder status achieved in 
Study I4V-MC-JAIW (JAIW).

Proportion of patients achieving IGAEASI75 from 
baseline of 0 or 1originating study, assessed at 
Week 16
Secondary
To describe the clinical response to baricitinib 2-mg 
QD in AD as measured by improvement in signs and 
symptoms of AD by prior treatment received (ie., 
baricitinib 2-mg, 1-mg, or placebo) received and 
responder status achieved in Study JAIW.

Proportion of patients achieving IGA of 0 or 1 
assessed at Week 16 

Proportion of patients achieving IGA of 0 or 1 
assessed at or before Week 16

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at Week 16

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at or before 
Week 16

Mean percent change from baseline in EASI score 
from baseline of originating study, assessed at 
Week 16 

Proportion of patients achieving a BSA of ≤3% 
assessed at or before Week 16
To describe the clinical response to baricitinib 2-mg 
QD in AD as assessed by patient-reported outcome 
measures by prior treatment received (ie., baricitinib 
2-mg, 1-mg, or placebo) received and responder 
status achieved in Study JAIW.

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 
originating study, assessed at Week 16

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 
originating study, assessed at or before Week 16

Mean percent change from baseline of originating 
study, in Itch NRS assessed at Week 16
Abbreviations:  AD = atopic dermatitis; BSA = body surface area; EASI = Eczema Area and Severity Index; 
EASI75 = 75% improvement from baseline in EASI; IGA = Investigator’s Global Assessment; NRS = numeric 
rating scale; QD = once daily.
Summary of Study Design:
Study I4V-MC-JAIX (JAIX) is a Phase 3, multicenter, open-label outpatient study evaluating the efficacy and safety 
of baricitinib 2-mg once daily (QD) in adult patients with moderate to severe AD.  The study population will include 
patients 18 years or older with a history of inadequate response or intolerance to existing topical therapies, and who 
have completed at least Visit 8protocol-defined minimal participation in Study JAIW based on responder status.

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The study duration will be up to 108204 weeks over 2 study periods:

Period 1:  Open-Label Treatment Period, lasting from Week 0 (baseline, Visit 1) through Week 104200
(Visit 1117).
Period 2:  Post-Treatment Follow-Up Period (Visit 801), spanning the period from the last treatment visit at 
Week 104200 (Visit 1117) or Early Termination Visit (ETV) to approximately 4 weeks following the last dose of 
investigational product
Treatment Arms and Duration:
Patients will be assigned at baseline to open-label treatment with baricitinib 2-mg QD.  The study duration will be 
up to 108204 weeks (Open-Label Treatment Period:  104200 weeks; Post-Treatment Follow-Up Period:  
approximately 4 weeks after the last dose of investigational product).
Number of Patients:
This study will include approximately 300up to 450 patients with AD who will be treated with baricitinib 2-mg QD.
Statistical Analysis:
Unless otherwise specified, the efficacy and health outcomes summaries will be conducted on all enrolled patients
who receive at least 1 dose of investigational product in Study JAIX, even if the patient does not follow the protocol, 
and safety analyses will be conducted on all enrolled patients who receive at least 1 dose of investigational product
and who do not discontinue from the study for the reason “Lost to Follow-up” at the first postbaseline visit.  
Treatment comparisons of discrete efficacy variables between prior-treatment-received groups may be performed 
using group percentages.    All patients who discontinue the study or study treatment at any time for any reason will 
be defined as nonresponders for the nonresponder imputation (NRI) analysis for categorical variables after 
discontinuation onward.  
Continuous efficacy variables will be descriptively summarized in terms of number of patients, mean, standard 
deviation, median, minimum, and maximum.   
Frequencies and percentages will be computed for adverse event (AE), discontinuation, and other categorical safety 
data.  Continuous vital signs, body weight, and other safety variables including laboratory variables will be 
summarized by mean, standard deviation, median, minimum and maximum.  

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b
An ET visit should be conducted if a patient discontinues from the study before Week 104200.  Early termination visit activities do not need to be duplicated 
if occurring at the time of a scheduled visit. Weighing of TCS and collection of HADS, EQ-5D-5L, and WPAI-AD are not a component of study visit 17, only 
the ETV at or before Week 104.
c
Visit 801 is the PTFU visit, which occurs after the patient has been off baricitinib/IP for approximately 4 weeks.  Patients who have permanently discontinued 
IP but remain in the study for more than 28 days without IP will only complete Visit 1117/ET; Visit 801 (follow-up visit) is not required.
d
Screening should occur during the LPV of the originating study.   It may be permissible for screening to occur after the last visit of the originating study if 
needed, upon approval from the sponsor.
e Applies to ET visit if conducted prior to Week 16 only.
f
Only required at investigator discretion. Sponsor provided low potency TCS will be available to dispense to patients at anytime prior to study visit 11.  At 
visit 11 and after, low potency TCS is allowed as background therapy but will not be provided by the sponsor or reimbursed by the sponsor.  
g
The following measures (POEM, DLQI, HADS, EQ-5D-5L, WPAI-AD) should be completed prior to any clinical assessments being performed on days when
study visits occur.
h
Suicidal ideation and behavior subscales excerptadapted for the assessment of 11 preferred ideation and behavior categories.
i
The Self-Harm Follow-Up Form is required only if triggered by the Self-Harm Supplement Form.
j
Fasting lipid profile.  Patients should not eat or drink anything except water for 12 hours prior to sample collection.  If a patient attends these visits in a 
nonfasting state, this will not be considered a protocol violation.  Unscheduled lipid testing can be performed at the discretion of the investigator.
k
If laboratory examinations have been performed ≤4 weeks from previous study visit, then they do not need to be repeated.
l
For ET visits, collect fasting lipids when possible. 
m Clinical chemistry will include the following value calculated from serum creatinine:  estimated glomerular filtration rate (eGFR; calculated using the Chronic 
Kidney Disease Epidemiology Collaboration [CKD-EPI] Creatinine 2009 equation).
n
Patients who are positive for HBcAb and negative for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive as determined at screening 
of originating study, Study JAIW, regardless of HBsAb status or level, must undergo HBV DNA testing per the schedule.
o
Urinalysis, serum IgE, exploratory storage samples, and RNA and biomarker samples are only collected for ET visits occurring at or before Week 104.  These 
samples are not collected as a component of Visit 17For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at all 
specified visits.  If required per local regulations and/or institutional guidelines, pregnancy testing can occur at other times during the study treatment period.
p
For all women of childbearing potential, urine pregnancy tests (local laboratory) will be performed at all specified visits.  If required per local regulations 
and/or institutional guidelines, pregnancy testing can occur at other times during the study treatment period.

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3.2
Study Rationale
The recently completed Phase 2 study of baricitinib in AD, Study JAHG, met its primary 
objective of proportion of patients achieving a 50% improvement from baseline in Eczema Area 
and Severity Index (EASI50) scores compared to placebo.  Baricitinib also showed statistically 
significant improvements for other disease severity analyses as well as multiple different patient 
reported outcome scales compared to placebo, further validating the hypothesis that JAK1/JAK2 
signaling plays a key role in AD pathogenesis. Phase 3 placebo-controlled studies are ongoing to 
define baricitinib efficacy in AD.  This open-label, long-term extension study is designed to 
further assess long-term efficacy and safety of baricitinib in patients with moderate to severe 
AD, who did not achieve the primary end point (Investigator’s Global Assessment [IGA] 0, or 1)
in the originating study, Study I4V-MC-JAIW (JAIW).  This will allow patients originally 
randomized to baricitinib 1-mg or placebo in Study JAIW to have the opportunity for treatment 
with baricitinib 2-mg QD, and also assess the longer-term clinical utility of the 2-mg dose 
beyond achieving an IGA 0,1.  In addition, this study will give patients completing Study JAIW 
as responders the opportunity for ongoing access to baricitinib 2-mg.
4.
Objectives and Endpoints
Table JAIX.2.
Objectives and Endpoints
Objectives
Endpoints
Primary
To describe the clinical response to baricitinib 2-mg 
QD in patients with moderate to severe AD by prior 
treatment received (ie., baricitinib 2-mg, 1-mg, or 
placebo) received and responder status achieved in 
Study I4V-MC-JAIW (JAIW).) 

Proportion of patients achieving IGAEASI75 from 
baseline of 0 or 1originating study, assessed at 
Week 16
Secondary
To describe the clinical response to baricitinib 2-mg 
QD in AD as measured by improvement in signs and 
symptoms of AD by prior treatment received (ie., 
baricitinib 2-mg, 1-mg, or placebo) received and 
responder status achieved in Study JAIW.

Proportion of patients achieving IGA of 0 or 1 
assessed at Week 16

Proportion of patients achieving IGA of 0 or 1 
assessed at or before Week 16

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at Week 16

Proportion of patients achieving EASI75 from 
baseline of originating study, assessed at or before 
Week 16

Mean percent change from baseline in EASI score 
from baseline of originating study, assessed at 
Week 16 

Proportion of patients achieving a BSA of ≤3% 
assessed at or before Week 16
To describe the clinical response to baricitinib 2-mg 
QD in AD as assessed by patient-reported outcome 

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 

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Objectives
Endpoints
measures by prior treatment received (ie., baricitinib 
2-mg, 1-mg, or placebo) received and responder 
status achieved in Study JAIW.
originating study, assessed at Week 16

Proportions of patients achieving a ≥4-point 
improvement in Itch NRS from baseline of 
originating study, assessed at or before Week 16

Mean percent change from baseline of originating 
study, in Itch NRS assessed at Week 16
Exploratory Objectives/Endpoints

Exploratory objectives may include evaluating the response to baricitinib treatment regimens on clinical 
measures and patient reported outcomes.  These endpoints may include dichotomous endpoints or change 
from baseline for the following measures:  IGA, EASI, SCORAD, POEM, HADS, DLQI, WPAI-AD, EQ-
5D-5L, Itch NRS, ADSS Item 2 score, Skin Pain NRS, PGI-S-AD.

To evaluate changes from baseline in IgE levels during the study.

To evaluate changes from baseline in eosinophil levels during the study.  
Abbreviations:  AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BSA = body surface area; DLQI = 
Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; EASI75 = 75% improvement from 
baseline in EASI; EQ-5D-5L = the European Quality of Life–5 Dimensions–5 Levels; HADS = Hospital Anxiety 
Depression Scale; IGA = Investigator’s Global Assessment; IgE = immunoglobulin E; NRS = numeric rating 
scale; QD = once daily; PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; POEM = 
Patient-Oriented Eczema Measure; SCORAD = SCORing Atopic Dermatitis; WPAI-AD = Work Productivity 
and Activity Impairment – Atopic Dermatitis.
5.
Study Design
5.1
Overall Design
Study I4V-MC-JAIX (JAIX) is a Phase 3, multicenter, open-label, outpatient study evaluating 
the efficacy and safety of baricitinib 2-mg QD in adult patients with moderate to severe AD.  The 
study is divided into 2 periods; a 104200-week Open-Label Treatment period, and a 4-week 
Post-Treatment Follow-Up period. The following patients will be eligible to participate in this 
study:

Partial Responders (IGA 2 at Week 16 of Study JAIW)

Previous Responders at Week 16 of Study JAIW (IGA 0 or 1): Patients who were 
responders at Week 16 of Study JAIW, and thus remain in Study JAIW but later 
experience loss of response resulting in an IGA ≥3 (or requiring more than low-potency 
TCS after Week 16 to manage symptoms)

Nonresponders (IGA 3 or 4 at Week 16 of Study JAIW or rescued with topical [e.g. TCS, 
TCNI] or systemic therapies prior to Week 16)

Responders who completed Study JAIW through Week 104 (Visit 15)
Approximately 300 patients who have been discontinued from Study JAIW may be eligible to 
enroll in this study.  Patients who complete Study JAIW through Visit 8 (Week 16) can enter 
Study JAIX.  In addition, patients who complete Study JAIW as responders may be eligible to 
enroll in this study.  For most patients, the last visit of the originating study will be the first visit 
and screening/baseline period for Study JAIX.  Patients will have been using emollients daily in 

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their originating study and this will continue during Study JAIX participation. Starting at 
baseline, patients will be treated with open-label baricitinib 2-mg QD for up to 104200 weeks.
All procedures to be conducted during the study, including timing of all procedures, are indicated 
in the Schedule of Activities (Section 2).  Section 9.4.3 describes collection of laboratory 
samples; Appendix 2, Appendix 4, Appendix 5, and Appendix 6 list the specific laboratory tests 
that will be performed for this study.  Study governance considerations are described in detail in 
Appendix 3. The IGA tool to be used in this study is included in Appendix 8.
Figure JAIX.1 illustrates the study design.  The dosing regimen is described in Section 7.1. 
Abbreviations:  AD = atopic dermatitis; QD = once daily; V = visit; W = week.
a
Occurs approximately 28 days after the last dose of investigational product.
Figure JAIX.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIX.

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5.1.1.Period 1:  Open-Label Treatment, Weeks 0 to 200104
Screening should occur during the last visit of the originating study. Study eligibility for each 
patient will be reviewed based on all enrollment criteria (Section 6). Patients who meet all 
criteria will have treatment allocated by interactive web-response system (IWRS) and begin their 
treatment period at Visit 1. Patients who meet all of the inclusion and none of the exclusion 
criteria (Section 6) will be enrolled in the study.  It may be permissible for screening to occur 
after the last visit of the originating study if needed, upon approval from the sponsor. For 
example, patients requiring elective procedures may want to have those in between studies.  , or 
responders who complete Visit 15 of Study JAIW have the option to delay enrollment into open-
label Study JAIX to assess response while off investigational product.
Patients who received oral systemic AD treatment and/or topical rescue therapy during the 
originating study must discontinue use of the prohibited medications listed in Section 7.7.1 prior 
to initiating IP in Study JAIX.  Low-potency TCS (e.g., hydrocortisone 2.5% ointment) is 
permitted (Section 7.7.2).
Patients will receive open-label baricitinib 2–mg QD.  Investigational product will be 
administered daily for a maximum of 104200 weeks (treatment period Visits 1 through 1117; see 
Section 7).  All patients will be required to use emollients daily.  Daily diaries will continue to be 
utilized through Week 16.  Download of this data will be required at study visits.  Patients are 
allowed to use low potency TCS (e.g., hydrocortisone 2.5% ointment) in combination with 
investigational product.  Rescue with higher potency TCS, topical calcineurin inhibitors 
(TCNIs), or systemic therapies is not allowed.  Assessments of disease severity will be 
performed by the investigator as described in the Schedule of Activities (Section 2).
The primary efficacy endpoint will be at Week 16 (Visit 4).  All patients who permanently 
discontinue investigational product prior to the primary endpoint should complete an ETV and 
post-treatment follow-up visit.  
At Week 16, all patients should be formally assessed to determine if sufficient clinical benefit 
has been observed to justify continuing in this study.  Clinical benefit is defined as meeting at 
least 1 of the following criteria during the first 16 weeks:

IGA score of 0 or 1 with a ≥2-point improvement from baseline of originating study, 

≥4-point improvement from baseline of originating study in Itch NRS, 

EASI-75 from baseline of originating study, or

BSA involvement of ≤3%. 
If a patient achieves any of these treatment goals during the first 16 weeks of the treatment 
period, the patient will be allowed to continue in the study. Although formal criteria for 
sufficient clinical benefit should be assessed at Week 16, investigators are strongly encouraged 
to discontinue patients who have not shown signs of clinical benefit by Week 8 of Study JAIX, 
defined as improvement in IGA, itch NRS, EASI, or BSA. Attention should be given to patients 
treated continuously for 16 weeks during Study JAIW (no IP discontinuation for systemic rescue 

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therapy) and who then show no benefit in Study JAIX, to avoid exposing patients to a potentially 
ineffective therapy for an additional 16 weeks before discontinuation.  Since no rescue therapies 
are available during this study, patients requiring more than low-potency TCS at any time during 
the study will be discontinued.
5.1.2.Period 2:  Post-Treatment Follow-Up
Patients who complete the study through Visit 1117 (Week 104200) will have a post-treatment
follow-up visit (Visit 801) approximately 28 days after the last dose of investigational product.
Patients who have received at least 1 dose of investigational product and discontinue early from 
the study should have an ETV, and return for the post-treatment safety follow-up visit (Visit 801) 
approximately 28 days after the last dose of investigational product.
Patients who have discontinued investigational product but remain in the study for more than 
28 days without investigational product will have an ETV if they choose to discontinue early; 
however, a separate follow-up visit (V801) is not required.
Patients should not initiate new systemic AD treatment during this period.  However, if patients 
or investigators must initiate treatment, investigators should make every attempt to conduct 
efficacy and safety assessments immediately before administering any new treatment. 
An unscheduled visit can be used for this purpose if necessary. 
5.2.
Number of Participants
Approximately 300Up to 450 participants willmay be enrolled, although final number of patients 
will be determined by response rate observed in the originating Study JAIW.
5.4.
Scientific Rationale for Study Design
This open-label long-term extension study will enroll moderate to severe AD patients who have 
completed treatment visits until at least the primary endpoint of an originating study (i.e., Visit 8, 
Week 16 of Study JAIW) but who did not achieve the primary endpoint of IGA 0,1, or who 
experience loss of response after Week 16, or who complete Study JAIW as responders at Visit 
15, Week 104. This study will further assess long-term efficacy and safety of baricitinib in this 
population.  This will allow patients originally randomized to baricitinib 1-mg or placebo in 
Study JAIW to have the opportunity for treatment with baricitinib 2-mg QD, and also assess the 
longer-term clinical utility of the 2-mg dose beyond achieving an IGA 0,1.
During the open-label treatment period, patients will be treated with baricitinib 2-mg, which has 
been shown to be efficacious in the Phase 2 study in AD (JAHG). Patients will also be allowed 
to use low-potency TCS (e.g., hydrocortisone 2.5% ointment) as background therapy for comfort 
if needed. Daily treatment with emollient will continue. To avoid confounding effect of topical 
therapies, higher-potency TCS, as well as TCNIs and topical phosphodiesterase type 4 (PDE-4) 
inhibitors are not allowed at any time during the study. If a patient does not experience sufficient 
clinical benefit during the study, the patient should be discontinued.  The criteria for determining 
sufficient clinical benefit are discussed in Section 5.1.1.  This 24-year-long study will generate
important long-term efficacy and safety data in AD.

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The post-treatment follow-up period (Period 2) is for safety monitoring after the patient has been 
off investigational product for approximately 28 days.
6. Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
The study population will comprise patients diagnosed with AD who have completed at least 
Visit 8 (Week 16) of Study JAIW.  Study investigator(s) will determine if the patient meets all 
inclusion criteria and none of the exclusion criteria to qualify for enrollment in the study.  All 
screening activities must be completed and reviewed before the patient is enrolled.
6.1.
Inclusion Criteria
Type of Patient and Disease Characteristics
[1]
have completed the minimum number of visits based on responder status in 
Study JAIW

nonresponder/partial responder: have completed at least 16 weeks of 
treatment in Study JAIW (i.e., Visit 8, Week 16) and
A nonresponder/partial responder is defined as a patient who met at least 1 
of the following in Study JAIW: 

did not achieve an IGA of 0 or 1 at Week 16, or

achieved an IGA ≥3 after Week 16, or

required rescue therapy at any time.
or

responder: have completed the full treatment period of Study JAIW (i.e., 
Visit 15, week 104)
A responder is defined as a patient who achieved IGA 0 or 1 and who did 
not require rescue therapy at or before Week 16 in Study JAIW.
7.6
Treatment Compliance
Patient compliance with study medication will be assessed at each visit during the treatment 
period (Visit 2 through Visit 1117) by counting returned tablets.  
A patient will be considered significantly noncompliant if he or she misses more than 20% of the 
prescribed doses of investigational product during the study, unless the patient’s investigational 
product is withheld by the investigator for safety reasons.  Similarly, a patient will be considered 
significantly noncompliant if he or she is judged by the investigator to have intentionally or 
repeatedly taken 20% more than the prescribed amount of medication during the study.
Patients will be counseled by study staff on the importance of taking the investigational product 
as prescribed, as appropriate.

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Patients’ compliance will be further defined in the statistical analysis plan (SAP).
7.7.3. Rescue Therapy
No rescue therapy options are available during the study.  Patients are allowed to use low-
potency TCS as background therapy for comfort if needed. Patients who experience worsening 
and unacceptable symptoms of AD should consider discontinuing from the study.  Patients 
requiring more than low-potency TCS to manage their symptoms should also be discontinued.
Hydrocortisone 2.5% ointment will be supplied by the sponsor. for use during the first 2 years of 
the treatment period (dispensed at Visits 1-10 only).  In the event that providing this topical 
formulation during the first 2 years is not possible, an alternate, equivalent potency TCS cream 
and/or ointment may be provided by the sponsor.  Use of sponsor-supplied TCS should be 
recorded via weight of returned tubes as indicated in the Schedule of Activities (Section 2).  
Sponsor will not provide or reimburse the cost of TCS at Visit 11 or after.
In the event that the sponsor is unable to supply TCS during the first 2 years of the treatment 
period, commercially available hydrocortisone 2.5% ointment or an equivalent-potency TCS 
cream and/or ointment that is in line with local practices can be supplied by the sponsor or the 
sites. Refer to Appendix 7 for guidance on potency equivalence.  
On the days of study visits, topical therapy should not be applied before the patient has 
undergone all study procedures and clinical evaluations to allow adequate assessment of skin 
dryness.
8.2
Discontinuation From the Study 
Patients may choose to withdraw from the study for any reason at any time, and the reason for 
early withdrawal will be documented.
Some possible reasons that may lead to permanent discontinuation include the following:

enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study

participation in the study needs to be stopped for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and good clinical 
practice

study termination may occur in a specific country or region when baricitinib is approved 
for the treatment of AD and becomes reimbursed or commercially available in that 
country or region, or a negative regulatory opinion is received in that country or region  

investigator decision
o
The investigator decides that the patient should be discontinued from the 
study.

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o
If the patient, for any reason, requires treatment with another therapeutic 
agent (not allowed as part of rescue therapy [Section 7.7.3]) that has been 
demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new 
agent.

patient 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 per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol.
9.1.1 Primary Efficacy Assessments
Eczema Area and Severity Index Scores (EASI): The EASI assesses extent of disease at 4
body regions and measures 4 clinical signs:  (1) erythema, (2) induration/papulation, (3) 
excoriation, and (4) lichenification, each on a scale of 0 to 3.  The EASI confers a maximum 
score of 72.  The EASI evaluates 2 dimensions of AD:  disease extent and clinical signs (Hanifin 
et al. 2001).Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA AD):  
The IGA used in this study, the vIGA AD (referred to as the IGA throughout the protocol) 
measures the IGA of the patient’s overall severity of their AD, based on a static, numeric 5 point 
scale from 0 (clear skin) to 4 (severe disease).  The score is based on an overall assessment of the 
degree of erythema, papulation/induration, oozing/crusting, and lichenification.
9.1.2 Secondary Efficacy Assessments
9.1.2.1. Eczema Area and Severity Index scoresValidated Investigator’s Global 
Assessment for Atopic Dermatitis (vIGA-AD)
The IGA used in this study, the vIGA-AD (referred to as the IGA throughout the protocol) 
measures the IGA of the patient’s overall severity of their AD, based on a static, numeric 5-point 
scale from 0 (clear skin) to 4 (severe disease).  The score is based on an overall assessment of the 
degree of erythema, papulation/induration, oozing/crusting, and lichenification.
9.1.2.12. Eczema Area and Severity Index scores
9.1.2.23. SCORing Atopic Dermatitis
9.1.2.34. Hospital Anxiety Depression Scale
10.1. Sample Size Determination
It is anticipated that approximately 90% of enrolled patients will complete Week 16 of 
Study JAIW; of these patients, it is expected that approximately 75% will roll over into 
Study JAIX.  Assuming that approximately 90% of the nonresponders and partial responders join 
Study JAIX, then the planned enrollment will be approximately 300 patients.  The study is 

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descriptive in nature and the sample size is not based on any statistical power calculations.  The 
final sample size will depend on the response rate in Study JAIW.All of the approximate 450 
patients participating in the originating study can be assessed for eligibility to participate in 
Study JAIX.
10.3.1 General Statistical Considerations
As this study is open-label and all patients are receiving baricitinib 2-mg, no hypothesis testing 
will be performed.  Data will be summarized both overall and by prior-treatment-received in 
Study JAIW. Data from this trial may be integrated with other trials.
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.
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 (CSR).  Additional exploratory analyses of the data will be conducted 
as deemed appropriate.
All discrete efficacy variables will be summarized using frequencies and percentages.  
Continuous efficacy and health outcome variables will be summarized using number of patients, 
mean, standard deviation, median, minimum, and maximum.
The methods used to handle missing data will be specified in the SAP.
Frequencies and percentages will be computed for AEs, discontinuation, and other categorical 
safety data. Continuous vital signs, body weight, and other safety variables including laboratory 
variables will be summarized using mean, standard deviation, median, minimum and maximum.  
Shift tables for categorical safety analyses (e.g., “high” or “low” laboratory results) will also be 
produced.
All patients who discontinue the study or the study treatment at any time for any reason will be 
defined as nonresponders for the NRI summary of categorical efficacy variables such as IGA 0/1 
or EASI 50/75/90 after discontinuation and onward.  
10.3.4. Safety Analyses
All safety data will be summarized overall and by prior therapy received using the safety 
population.
Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred or worsened 
in severity after the first dose of study treatment. The number of TEAEs as well as the number 
and percentage of patients who experienced at least 1 TEAE will be summarized using Medical 
Dictionary for Regulatory Activities (MedDRA) for each system organ class (or a body system) 
and each preferred term. Serious adverse events and AEs that lead to discontinuation of 
investigational product will also be summarized. 

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Categorical variables, including the incidence of AEs of special interest, together with individual 
analyses of clinical laboratory results and vital signs are not planned for this Study, but will be 
included in an integrated database.
All clinical laboratory results will be descriptively summarized.  Additional summary may be 
produced by prior treatment received.  Individual results that are outside of normal reference 
ranges will be flagged in data listings.  Quantitative clinical hematology, chemistry, and 
urinalysis variables obtained at the baseline to postbaseline visits will be summarized as changes 
from baseline.  Categorical variables, including the incidence of abnormal values and incidence 
of AEs of special interest, will be summarized by frequency and percentage of patients in 
corresponding categories.  Shift tables will be presented for selected measures.
Observed values and changes from baseline (predose or screening if missing) for vital signs and 
physical characteristics will be summarized by visit.  Change from baseline to postbaseline in 
vital signs, and body weight will be summarized using mean, standard deviation, median, 
minimum, and maximum.  The incidence and average duration of investigational product 
interruptions will be summarized. Various techniques may be used to estimate the effects of 
investigational product interruptions on safety measures.  Further summaries may be performed 
and will be planned in the SAP.
Data collected after initiation of rescue therapy will be summarized as appropriate.

Leo Document ID = c2a9e61c-547d-4bef-81eb-2753ad40062b
Approver: 
Approval Date & Time: 28-Oct-2019 16:36:52 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 28-Oct-2019 21:37:07 GMT
Signature meaning: Approved
PPD
PPD