A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Safety and Efficacy of Baricitinib in Combination With Topical Corticosteroids in Adult Patients With Moderate-to-Severe Atopic Dermatitis Who Have Experienced Failure to Cyclosporine or Are Intolerant to, or Have Contraindication to, Cyclosporine
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

Protocol (e) I4V-MC-JAIN 
 
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the 
Safety and Efficacy of Baricitinib in Combination with Topical Corticosteroids in Adult Patients 
with Moderate-to-Severe atopic Dermatitis Who Have Experienced Failure to Cyclosporine or 
Are Intolerant to, or Have Contradiction to Cyclosporine 
 
NCT03428100 
 
Approval Date: 06-Dec-2019 

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Protocol I4V-MC-JAIN(e)
A Phase3,Multicenter, Double-Blind, Randomized, 
Placebo-Controlled Study Evaluating the Safety and Efficacy 
of Baricitinibin Combination with Topical Corticosteroids in 
Adult Patients with Moderate-to-Severe Atopic Dermatitis 
WhoHave Experienced Failure to Cyclosporine or Are 
Intolerant to, or Have Contraindication to,Cyclosporine
BREEZE-AD4
EUDRA CTA 2017-004574-34
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 clinicalinvestigation of
baricitinib (LY3009104), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Approval Date: 06-Dec-2019 GMT
Baricitinib (LY3009104)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
ProtocolElectronicallyS
igned andApprovedby Lilly on 09-Nov-2017
Amendment (a) Electronically Signed and Approved by Lilly on 15-Dec-2017
Amendment (b) Electronically Signed and Approved by Lilly on 01 Oct 2018
Amendment (c) Electronically Signed and Approved by Lilly on 09 May 2019
Amendment (d) Electronically Signed and Approved by Lilly on 30 Sep 2019
Amendment (e) Electronically Signed and Approved by Lilly on date provided below

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Table of Contents
Section
Page
Protocol I4V-MC-JAIN(e) A Phase 3, Multicenter, Double-Blind, 
Randomized, Placebo-Controlled Study Evaluating the Safety and 
Efficacy of Baricitinib in Combination with Topical Corticosteroids 
in Adult Patients with Moderate-to-Severe Atopic Dermatitis Who 
Have Experienced Failure to Cyclosporine or Are Intolerant to, or 
Have Contraindication to, Cyclosporine  BREEZE-AD4.....................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................16
3.
Introduction ......................................................................................................................23
3.1.
Background..................................................................................................................23
3.2.
Benefit/Risk Assessment..............................................................................................24
3.3.
Study Rationale............................................................................................................25
4.
Objectives and Endpoints..................................................................................................27
5.
Study Design.....................................................................................................................30
5.1.
Overall Design .............................................................................................................30
5.1.1.
Period 1:  Screening and Baseline Period .............................................................32
5.1.2.
Period 2:  Double-Blind Placebo-Controlled Treatment........................................33
5.1.3.
Period 3:  Double-Blind, Long-Term Extension ...................................................33
5.1.3.1.
Randomized Downtitration Substudy at Week 52 ...........................................33
5.1.3.2.
Patients Not Eligible for the Substudy ............................................................34
5.1.4.
Period 4: Bridging Extension ...............................................................................35
5.1.5.
Period 5:  Post-Treatment Follow-Up...................................................................35
5.2.
Number of Participants.................................................................................................36
5.3.
End of Study Definition ...............................................................................................36
5.4.
Scientific Rationale for Study Design...........................................................................36
5.5.
Justification for Dose ...................................................................................................37
5.5.1.
Rationale for Dose Adjustment for Renal Impairment ..........................................38
6.
Study Population...............................................................................................................39
6.1.
Inclusion Criteria..........................................................................................................39
6.2.
Exclusion Criteria ........................................................................................................42
6.3.
Lifestyle Restrictions....................................................................................................48
6.4.
Screen Failures.............................................................................................................48
7.
Treatments........................................................................................................................49
7.1.
Treatments Administered .............................................................................................49

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7.1.1.
Packaging and Labeling .......................................................................................49
7.2.
Method of Treatment Assignment ................................................................................50
7.2.1.
Selection and Timing of Doses.............................................................................50
7.2.2.
Dose Adjustment for Renal Impairment ...............................................................50
7.3.
Blinding .......................................................................................................................51
7.4.
Dosage Modification....................................................................................................51
7.5.
Preparation/Handling/Storage/Accountability...............................................................51
7.6.
Treatment Compliance .................................................................................................51
7.7.
Concomitant Therapy...................................................................................................52
7.7.1.
Permitted Medications and Procedures.................................................................52
7.7.2.
Use of Topical Corticosteroids .............................................................................53
7.7.3.
Use of Antihistamines..........................................................................................54
7.7.4.
Prohibited Medications and Procedures................................................................56
7.7.5.
Rescue Therapy....................................................................................................57
7.7.5.1.
Rescue during Period 2:  Week 0 (Visit 2) up to Week 52 
(Visit 14)........................................................................................................57
7.7.5.2.
Rescue during Periods 3 and 4:  from Week 52 (Visit 14) 
to Week 200 (Visit 28) ...................................................................................58
7.8.
Treatment after the End of the Study............................................................................58
8.
Discontinuation Criteria ....................................................................................................59
8.1.
Discontinuation from Study Treatment.........................................................................59
8.1.1.
Temporary Interruption of Investigational Product ...............................................59
8.1.2.
Permanent Discontinuation from Investigational Product .....................................60
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................61
8.2.
Discontinuation from the Study....................................................................................62
8.3.
Lost to Follow-Up........................................................................................................62
9.
Study Assessments and Procedures ...................................................................................63
9.1.
Efficacy Assessments...................................................................................................63
9.1.1.
Primary Efficacy Assessment...............................................................................63
9.1.2.
Secondary Efficacy Assessments..........................................................................63
9.1.2.1.
Validated Investigator’s Global Assessment for Atopic 
Dermatitis (vIGA AD)....................................................................................63
9.1.2.2.
SCORing Atopic Dermatitis ...........................................................................63
9.1.3.
Health Outcomes and Quality-of-Life Measures...................................................63
9.1.3.1.
Hospital Anxiety Depression Scale.................................................................64
9.1.3.2.
Patient-Oriented Eczema Measure ..................................................................64
9.1.3.3.
Itch Numeric Rating Scale..............................................................................64
9.1.3.4.
Atopic Dermatitis Sleep Scale ........................................................................64

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9.1.3.5.
Skin Pain Numeric Rating Scale .....................................................................64
9.1.3.6.
Patient Global Impression of Severity.............................................................64
9.1.3.7.
Dermatology Life Quality Index.....................................................................65
9.1.3.8.
European Quality of Life–5 Dimensions–5 Levels..........................................65
9.1.3.9.
Work Productivity and Activity Impairment 
Questionnaire–Atopic Dermatitis....................................................................65
9.1.3.10.
Medical Outcomes Study 36-Item Short Form Health 
Survey Version 2 Acute (SF-36).....................................................................66
9.1.4.
Appropriateness of Assessments ..........................................................................66
9.2.
Adverse Events ............................................................................................................66
9.2.1.
Serious Adverse Events........................................................................................67
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................68
9.2.2.
Adverse Events of Special Interest .......................................................................68
9.2.3.
Complaint Handling.............................................................................................68
9.3.
Treatment of Overdose.................................................................................................68
9.4.
Safety...........................................................................................................................68
9.4.1.
Electrocardiograms ..............................................................................................69
9.4.2.
Vital Signs ...........................................................................................................69
9.4.3.
Physical Examination...........................................................................................69
9.4.4.
Laboratory Tests ..................................................................................................69
9.4.5.
Columbia Suicide Severity Rating Scale...............................................................69
9.4.6.
Self-Harm and Follow-Up Supplement Forms......................................................70
9.4.7.
Chest x-ray and Tuberculosis Testing...................................................................70
9.4.8.
Hepatitis B Virus DNA Monitoring......................................................................70
9.4.9.
Safety Monitoring ................................................................................................70
9.4.10.
Hepatic Safety Monitoring ...................................................................................71
9.4.10.1.
Hepatic Safety Data Collection.......................................................................71
9.5.
Pharmacokinetics .........................................................................................................72
9.6.
Pharmacodynamics ......................................................................................................72
9.7.
Pharmacogenetics.........................................................................................................72
9.7.1.
Blood Samples for Pharmacogenetic Research .....................................................72
9.8.
Biomarkers...................................................................................................................72
9.9.
Medical Resource Utilization and Health Economics ...................................................73
10.
Statistical Considerations ..................................................................................................74
10.1. Sample Size Determination ..........................................................................................74
10.2. Populations for Analyses..............................................................................................74
10.3. Statistical Analyses ......................................................................................................74
10.3.1.
General Statistical Considerations ........................................................................74

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10.3.1.1.
Missing Data Imputation ................................................................................76
10.3.1.2.
Adjustment for Multiple Comparisons ............................................................76
10.3.1.3.
Adjustment for Unblinding of Primary Analyses 
24-Week Data.................................................................................................77
10.3.2.
Treatment Group Comparability...........................................................................77
10.3.2.1.
Patient Disposition..........................................................................................77
10.3.2.2.
Patient Characteristics ....................................................................................78
10.3.2.3.
Concomitant Therapy .....................................................................................78
10.3.2.4.
Treatment Compliance....................................................................................78
10.3.3.
Efficacy Analyses ................................................................................................78
10.3.3.1.
Primary Analyses ...........................................................................................78
10.3.3.2.
Secondary Analyses........................................................................................78
10.3.4.
Safety Analyses....................................................................................................80
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................80
10.3.6.
Other Analyses.....................................................................................................81
10.3.6.1.
Health Economics...........................................................................................81
10.3.6.2.
Subgroup Analyses.........................................................................................81
10.3.7.
Interim Analyses..................................................................................................81
10.3.7.1.
Data Monitoring Committee ...........................................................................81
10.3.7.2.
Adjudication Committee.................................................................................81
10.3.7.3.
Unblinded Study Team for the Primary Analyses for 
Regulatory Submission...................................................................................82
10.3.7.4.
Other Interim Analyses...................................................................................82
11.
References ........................................................................................................................83
12.
Appendices .......................................................................................................................87

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List of Tables
Table
Page
Table JAIN.1.
Schedule of Activities....................................................................................17
Table JAIN.2.
Objectives and Endpoints...............................................................................27
Table JAIN.3.
Treatment Regimens......................................................................................49
Table JAIN.4.
Medical and Laboratory Criteria for Temporary Interruption of 
Investigational Product ..................................................................................59

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List of Figures
Figure
Page
Figure JAIN.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIN. ...................32

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................88
Appendix 2.
Clinical Laboratory Tests...............................................................................92
Appendix 3.
Study Governance Considerations..................................................................94
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................98
Appendix 5.
Liver Function Testing and Hepatic Safety Monitoring..................................99
Appendix 6.
American Academy of Dermatology:  Criteria for the Diagnosis and 
Assessment of Atopic Dermatitis .................................................................100
Appendix 7.
Classification of Potency for Topical Corticosteroids...................................101
Appendix 8.
Monitoring Tests for Confirmed VTE..........................................................102
Appendix 9.
Protocol Amendment I4V-MC-JAIN(e) Summary 
A Phase 3, Multicenter, Double-Blind, Randomized, 
Placebo-Controlled Study Evaluating the Safety and Efficacy of 
Baricitinib in Combination with Topical Corticosteroids in Adult 
Patients with Moderate-to-Severe Atopic Dermatitis Who Have 
Experienced Failure to Cyclosporine or Are Intolerant to, or Have 
Contraindication to, Cyclosporine................................................................103

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1. Synopsis
Title of Study:
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the 
Safety and Efficacy of Baricitinib in Combination with Topical Corticosteroids in Patients with 
Moderate-to-Severe Atopic Dermatitis Who Have Experienced Failure to Cyclosporine or are 
Intolerant to, or have Contraindication to, Cyclosporine.
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 2008).  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.
Mild AD can be controlled by appropriate skin care and topical treatments; moderate and severe
AD usually require additional treatments such as phototherapy or systemic immunosuppressants 
(Wollenberg et al. 2016).  Cyclosporine A (CyA) has been approved for the treatment of patients 
with severe AD in Europe and for the treatment of patients with resistance to existing therapies 
in Japan and is used off-label in the United States (US) and other geographies (Bieber and 
Straeter 2015).  Cyclosporine A is usually considered a first-line option for patients requiring 
immunosuppressive treatment.  However, the safety profile of CyA limits its use to the 
short-term treatment of acute flares; for chronic severe AD, treatment duration should not exceed 
1 year (Bieber and Straeter 2015). Hence, there is a need for alternative therapy for patients with 
moderate-to-severe AD requiring systemic therapies.
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 2015).  This activity profile suggests that baricitinib would inhibit 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 (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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Objective(s)/Endpoints:
Objectives
Endpoints
Primary
To test the hypothesis that baricitinib 4-mg + TCS or 
baricitinib 2-mg + TCS is superior to placebo + TCS in 
the treatment of moderate–to-severe AD

Proportion of patients achieving EASI75 at 
Week 16
Key Secondary
These are prespecified objectives that will be adjusted for multiplicity
To test the hypothesis that baricitinib 1-mg + TCS is 
superior to placebo + TCS in the treatment of patients 
with moderate-to-severe AD

Proportion of patients achieving EASI75 at 
Week 16
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as measured by 
improvement of signs and symptoms of AD

Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at 16 weeks

Proportion of patients achieving EASI90 at
16 weeks

Percent change from baseline in EASI score at 
16 weeks

Proportion of patients achieving SCORAD75 at 
16 weeks
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as assessed by 
patient-reported outcome measures.

Proportion of patients achieving a 4-point 
improvement in Itch NRS at 16, 4, 2, and 
1 weeks

Mean change from baseline in the score of 
Item 2 of the ADSS at 16 weeks and 1 week.

Mean change from baseline in Skin Pain NRS 
at 16 weeks
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as measured by 
improvement of signs and symptoms of AD

Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement from baseline at 
Week 24

Proportion of patients achieving EASI75 at 24 
weeks
Other Secondary
These are prespecified objectives that will not be adjusted for multiplicity
To test the hypothesis that baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS is 
superior to placebo + TCS in the treatment of
moderate-to-severe AD

Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at Week 4 and 
Week 52.

Proportion of patients achieving EASI75 at 
Week 4 and Week 52
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as measured by 
improvement in signs and symptoms of AD

Proportion of patients achieving EASI50 at 
16 weeks

Proportion of patients achieving IGA of 0 at 
16 weeks

Mean change from baseline in SCORAD at 
16 weeks

Proportion of patients achieving SCORAD90 at 
16 weeks

Mean change from baseline in body surface 
area affected at 16 weeks

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
Proportion of patients developing skin 
infections requiring antibiotic treatment by 
Week 16

Mean number of days without use of 
background TCS over 16 weeks

Mean gram quantity of background TCS used 
over 16 weeks (tube weights)
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as assessed by 
patient-reported outcome measures

Percent change from baseline in Itch NRS at 
Weeks 52, 24, 16, 4, and 1

Proportion of patients achieving a 4-point 
improvement in Itch NRS at 24 weeks 

Mean change from baseline in the total score of 
the POEM at 16 weeks

Mean change from baseline in the PGI-S-AD 
scores at 16 weeks

Mean change from baseline in the HADS total 
scores at 16 weeks

Mean change from baseline in the DLQI total 
scores at 16 weeks

Mean change from baseline in the WPAI-AD
total scores at 16 weeks

Mean change from baseline in the EQ-5D-5L 
total scores at 16 weeks
Substudy:  Randomized Downtitration
These are prespecified objectives that will be not be adjusted for multiplicity
All Patients Entering the Substudy
To evaluate the change in clinical response after 
treatment downtitration from baricitinib

4-mg to 2-mg compared with patients who are 
rerandomized to remain on baricitinib 4-mg

2-mg to 1-mg compared with patients 
randomized to remain on baricitinib 2-mg
Patients Entering the Substudy with IGA 0 or 1
To evaluate the change in clinical response after 
treatment downtitration from baricitinib

4-mg to 2-mg compared with patients who are 
rerandomized to remain on baricitinib 4-mg

2-mg to 1-mg compared with patients 
randomized to remain on baricitinib 2-mg

Proportion of patients with a response of IGA 
0, 1, or 2 assessed at 16 weeks after 
rerandomization (Week 68) and Week 104

Proportion of patients with a response of IGA 0 
or 1 assessed at 16 weeks after rerandomization
(Week 68) and Week 104

Proportion of patients with a response of 
EASI75 from baseline assessed at 16 weeks 
after rerandomization (Week 68) and Week 104

Time to retreatment (time to IGA ≥3)
Patients Not Entered into Substudy
These are prespecified objectives that will not be adjusted for multiplicity
All Patients
1.
To evaluate the long-term effect of baricitinib 
dose on clinical measures
Patients with IGA 0 or 1
2.
To evaluate the long-term effect of baricitinib 
dose on clinical measures

Proportion of patients with a response of IGA 
0, 1, or 2 assessed at Weeks 68 and 104

Proportion of patients with a response of IGA 0 
or 1 assessed at Weeks 68 and 104

Proportion of patients with a response of 
EASI75 assessed at Weeks 68 and 104

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Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; DLQI = Dermatology Life Quality 
Index; EASI = Eczema Area and Severity Index; 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; PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; POEM = 
Patient-Oriented Eczema Measure; SCORAD = SCORing Atopic Dermatitis; TCS = topical corticosteroids; 
WPAI-AD = Work Productivity and Activity Impairment-Atopic Dermatitis.

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Summary of Study Design:
Study I4V-MC-JAIN (JAIN) is a Phase 3, multicenter, double-blind, randomized, 
placebo-controlled study evaluating the safety and efficacy of baricitinib 1-mg once daily (QD), 
2-mg QD, and 4-mg QD compared with placebo in patients with moderate-to-severe AD who are 
receiving background topical corticosteroid (TCS) treatment and who have experienced failure to 
cyclosporine or are intolerant to, or have a contraindication to, cyclosporine.
The study consists of 5 periods:
Period 1: Screening Period (Visit 1), up to 5 weeks prior to randomization
Period 2: 52-week Double-Blind Treatment Period: from Week 0 (Baseline; Visit 2) up 
to Week 52 (Visit 14)
Period 3: 52-week Double-Blind, Long-Term Extension Period: from Week 52 
(Visit 14) to Week 104 (Visit 22)
a.
Randomized Down-Titration Substudy (Week 52)
Responders who are eligible to enter the substudy will be rerandomized as 
follows:
baricitinib 4-mg treatment group 1:1 to baricitinib 2-mg, or baricitinib 
4-mg.
baricitinib 2-mg treatment group 1:1 to baricitinib 1-mg, or baricitinib 
2-mg.
b. Responders who are not eligible to enter the randomized downtitration will 
continue on the treatment regimen assigned at baseline; however, rerandomization 
to either 4-mg or 2-mg baricitinib is available for the placebo, baricitinib 2-mg, 
and 1-mg treatment groups if patients have a worsening of symptoms.
c.
Nonresponders in the placebo, baricitinib 2-mg, or baricitinib 1-mg treatment 
groups will be rerandomized at a 1:1 ratio to baricitinib 4-mg or baricitinib 2-mg 
QD at Week 52.  After rerandomization, patients will remain on the same dose of 
baricitinib for the remainder of the study.  Nonresponders who were randomized 
to baricitinib 4-mg will remain on 4-mg.
Period 4: Bridging Extension: from Week 104 (Visit 22) and up to Week 200 (Visit 28). 
Subjects who have completed Week 104 and have not met criteria of permanent 
discontinuation will have the possibility to remain in the trial for up to 96 
additional weeks (up to Week 200). 
Period 5: Post-Treatment Follow-Up Period: from last treatment period visit or early 
termination visit (ETV) to 4 weeks after the last dose of investigational product.
Treatment Arms and Duration:
At baseline, patients will be randomized at a 1:1:2:1 ratio to receive placebo QD, baricitinib 
1-mg QD, baricitinib 2-mg QD, or baricitinib 4-mg QD for up to 200 weeks.

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Number of Patients:
Planned enrollment is 500 patients ≥18 years of age.

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Statistical Analysis
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the 
intent-to-treat population and safety analyses will be conducted on those patients who receive at 
least 1 dose of investigational product.
Treatment comparisons of discrete efficacy variables will be made using a logistic regression 
analysis with treatment, baseline disease severity (vIGA AD) and baseline score in the model.  
Region may be added to the model if patient numbers allow.  The proportions and 95% 
confidence interval (CI) for the treatment comparisons will be reported.  If a patient needs to use 
rescue medication, the data from that point forward will be considered missing and missing data 
will be imputed using the nonresponder imputation (NRI) method.  Additional analyses will be
conducted using all observed data regardless of whether rescue medication was used or not.
Treatment comparisons of continuous efficacy and health outcome variables will be made using 
mixed-effects models for repeated measures (MMRM) model with treatment, baseline severity
(vIGA AD), visit, and treatment-by-visit interaction as fixed categorical effects and baseline 
score and baseline score-by-visit interaction as fixed continuous effects. Region may be added 
to the model if patient numbers allow.  An unstructured covariance matrix will be used to model 
the within-patient variance–covariance errors.  Type III sums of squares for the least squares 
means (LSMs) will be used for the statistical comparison and contrasts will be set up within the 
model to compare treatment groups at specific time points of interest.
Fisher exact test will be used for all adverse events (AEs), baseline, discontinuation, and other 
categorical safety data.  Continuous vital signs and laboratory values will be analyzed by an 
analysis of covariance (ANCOVA) with treatment and baseline values in the model.

I4V-MC-JAIN(e) Clinical Protocol
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2. Schedule of Activities

I4V-MC-JAIN(e) Clinical Protocol
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Table JAIN.1.
Schedule of Activities
Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
204
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
Inclusion and 
exclusion review
X
X
Informed consent
X
Clinical 
Assessments
Demographics
X
Medical history
X
Substance Use 
(alcohol, tobacco)
X
Previous and current 
AD treatments
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Vital signs (BP and 
Pulse)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical 
examination
X
Symptom-directed 
physical 
examinationb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG 
(single)
X
Chest x-rayc
(posterior–anterior 
view)
X
TB testd
X

I4V-MC-JAIN(e) Clinical Protocol
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Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
204
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
Read PPD if 
applicable (48 to 72 
hours after PPD)
Xe
Pre-existing 
Conditions
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO (patient diary) 
dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO (patient diary) 
returned
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Randomization/
rerandomizationg
X
Xg
IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP Dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP Returned and 
Compliance 
Assessed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weigh and dispense 
background TCS 
(tubes with cap)q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weigh and record 
returned background 
TCS (tubes with 
cap)q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Scales
IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Health Outcomes 
Measures and 
Other 

I4V-MC-JAIN(e) Clinical Protocol
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Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
204
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
Questionnairesh
Itch NRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Skin Pain NRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
ADSS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
PGI-S-AD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
POEM
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HADS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
EQ-5D-5L
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
WPAI-AD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
SF-36
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
C-SSRS and Self-
Harm Supplementi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-
Up Formj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory 
Assessments
Lipids (Fasting 
Visit)k
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical Chemistryl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancym
X
FSHn
X
TSH
X
HIV
X
HCV Antibodyo
X
HBV testing
X
HBV DNAp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAIN(e) Clinical Protocol
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LY3009104
Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
204
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
Urine Pregnancym
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacogenetics:  
blood
X
X
Serum 
immunoglobulin 
(IgE)
X
X
X
X
X
X
X
Xr
Exploratory storage 
samples (serum and 
plasma)
X
X
X
X
X
X
X
Xr
RNA and 
biomarkers:  blood
X
X
X
X
X
X
X
Xr
Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BP = blood pressure; C-SSRS = Columbia Suicide Severity Rating Scale 11 
categories suicidal ideation/suicidal behavior; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; ECG = electrocardiogram; 
EQ-5D-5L = the European Quality of Life–5 Dimensions 5 Levels; ET = early termination; ePRO = electronic patient-reported outcomes (device); 
FSH =  follicle-stimulating hormone; HADS = Hospital Anxiety Depression Scale; HCV = hepatitis C virus; HBV = hepatitis B virus; HIV = human 
immunodeficiency virus; ICF = informed consent form; IGA = Investigator’s Global Assessment; IgE = immunoglobulin E; IP = investigational product; 
IWRS = interactive web-response system; NRS = Numeric Rating Scale; PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; 
POEM = Patient-Oriented Eczema Measure; PPD = purified protein derivative; PTFU = post-treatment follow-up; SF-36 =Medical Outcomes Study 36-item 
short-form health survey; SCORAD = SCORing Atopic Dermatitis; TB = tuberculosis; TCS = topical corticosteroids; TSH = thyroid-stimulating hormone; 
V = visit; WPAI-AD = Work Productivity and Activity Impairment-Atopic Dermatitis.

I4V-MC-JAIN(e) Clinical Protocol
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a
An early termination visit should be conducted if patient discontinues from the study before Week 200. Visit 801 is the post-treatment follow-up visit, which 
occurs after the patient has been off baricitinib/study drug 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 28/ET; Visit 801 (follow-up visit) is not required.  ET visit activities do not need to be duplicated if 
occurring at the time of a scheduled visit. 
b
The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints.
c
A posterior–anterior chest x-ray will be performed at screening unless one has been performed within the past 6 months and the x-ray and reports are 
available.
d
TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®. See Exclusion Criterion [40] for description of TB testing. In countries where the 
QuantiFERON-TB Gold test or T-SPOT is available, either test may be used instead of the PPD TB test. The QuantiFERON-TB Gold test may be performed 
locally or centrally; the T-SPOT must be performed locally. (Note: Exception: Patients with a history of active or latent TB who have documented evidence 
of appropriate treatment, have no history of re-exposure since their treatment was completed, and have a screening chest x-ray with no evidence of active TB 
may be enrolled if other entry criteria are met. Such patients would not be required to undergo the protocol-specific TB testing but must have a chest x-ray at 
screening.)
e
If PPD testing was chosen to test for TB, then the patient must return and PPD test read 48 to 72 hours after Visit 1 (post-PPD).
f
Applies to ET Visit if conducted prior to Week 68 only.
g
At Week 52, patients who are eligible for the randomized downtitration substudy and nonresponders will be rerandomized as described in Section 5.1.3. 
h
The following measures (Itch NRS, Skin Pain NRS, ADSS, PGI-S-AD, POEM, DLQI, HADS, EQ-5D-5L, WPAI-AD, SF-36) should be completed prior to 
any clinical assessments being performed on days when study visits occur.
i
Suicidal ideation and behavior subscales excerpt – Adapted for the assessment of 11 preferred ideation and behavior categories.
j
The Self-Harm Follow-Up Form is required only if triggered by the Self-Harm Supplement Form.
k
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.
l
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).
m For all women of childbearing potential, a serum pregnancy test (central laboratory) will be performed at Visit 1.  Urine pregnancy tests (local laboratory) will 
be performed at Visit 2 and at all subsequent study visits after Visit 3.  If required per local regulations and/or institutional guidelines, pregnancy testing can 
occur at other times during the study treatment period.
n
For female patients ≥40 and <60 years of age who have had a cessation of menses for at least 12 months, an FSH test will be performed to confirm 
nonchildbearing potential (FSH ≥40 mIU/mL).
o
For patients who are positive for HCV antibody, a follow-up test for HCV RNA will be performed automatically.  Patients who are positive for HCV antibody 
and negative for HCV RNA may be enrolled.
p
Patients who are positive for HBcAb and negative for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive, regardless of HBsAb status 
or level, must undergo HBV DNA testing per the schedule.
q
Beyond Week 104, low and mid potency TCS will no longer be provided by the sponsor.
r
Only applicable to ET visits and V801 before Period 4. 

I4V-MC-JAIN(e) Clinical Protocol
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LY3009104
NOTE: Patients completing V22 and planning to sign the ICF for amendment (e) can participate as long as they have not completed 
a V801.

I4V-MC-JAIN(e) Clinical Protocol
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3. Introduction
3.1.
Background
Atopic dermatitis (AD), 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).  Atopic dermatitis causes pruritus 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, sleep quality and latency were significantly associated with poor 
quality of life (QoL) (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).
Whereas mild AD can be controlled by appropriate skin care and topical anti-inflammatory
treatments (topical corticosteroids [TCS] and topical calcineurin inhibitors [TCIs]), moderate and 
severe AD usually require additional treatments such as phototherapy or systemic 
immunosuppressants (Wollenberg et al. 2016).
Cyclosporine A (CyA) has been approved for the treatment of patients with severe AD in most 
European countries and for AD not controlled with existing therapies in Japan and is used 
off-label in the US and other geographies (Bieber and Straeter 2015). Cyclosporine A is usually 
considered a first-line option for patients requiring immunosuppressive treatment. However, the 
safety profile of CyA limits its use to the short-term treatment of acute flares; for chronic severe 
AD, treatment duration should not exceed 1 year (Bieber and Straeter 2015). Hence, there is a 
need for alternative therapy for patients with moderate-to-severe AD requiring systemic 
therapies, particularly those who have experienced failure to cyclosporine or are intolerant to, or 
have contraindication to, cyclosporine.
Until recently, there were no Food and Drug Administration (FDA)-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 interleukin (IL)-4 and IL-13, was approved by the FDA for this patient population
(Dupixent package insert, 2017).  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 (I4V-MC-JAHG [JAHG]) evaluated the safety and efficacy of baricitinib (a Janus 

I4V-MC-JAIN(e)Clinical Protocol
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LY3009104
kinase [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 Phase3 in patients with rheumatoid 
arthritis (RA) and in Phase2 in patients with diabetic nephropathy, moderate-to-severe psoriasis, 
and systemic lupus erythematosus.
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 administeredto 
patients with RA at doses up to 15-mg daily for 4weeks, 10-mg daily for 24weeks, 8-mg daily 
for 76weeks, and lower doses up to 4-mg daily for up to approximately 7years.  Through 13 
February 2019, nearly 3861patientshave been treated with baricitinib within the RA program at 
doses of 2-mg once daily (QD)or 4-mg QD. Of these, more than 2700patients have been 
treated with baricitinib for more than a year and more than 2100patients have been treated with 
baricitinib for more than 2years.
3.2. Benefit/Risk Assessment
CCI
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

I4V-MC-JAIN(e)Clinical Protocol
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LY3009104
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
More information about the known and expected benefits, risks, serious adverse events (SAEs), 
and reasonably anticipated adverse events (AEs) of baricitinib are to be found in the 
investigator’sbrochure (IB).
3.3. Study Rationale
CCI
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,but is only observed in about half of Caucasian patients 
whereasother variants of FLG are found in different ethnicities.(Palmer et al. 2006).  At a 
cellular level, AD is characterized by excessive T cell activation caused by genetic and 
environmentalfactors, leading to significant skin infiltration by T cells and dendritic cells.  The 
cytokine thymic stromal lymphopoietin (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).  Thymic stromal lymphopoietin and other key cytokines involved in AD pathogenesis, 
such as IL-4, IL-13, IL-5, IL-22, and IL-31, signal through receptors associated with intracellular 

I4V-MC-JAIN(e) Clinical Protocol
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LY3009104
JAK1/JAK2/tyrosine kinase 2 (TYK2) signaling (Ziegler et al. 2013; Nomura and Kabashima 
2015).
Janus kinases are a family of tyrosine kinases that mediate cytokine receptor signaling through 
phosphorylation and activation of signal transducers and activators of transcription (STAT) 
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 signaling 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; Zhong et al 
2014).

I4V-MC-JAIN(e) Clinical Protocol
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LY3009104
4.
Objectives and Endpoints
Table JAIN.2 shows the objectives and endpoints of the study.
Table JAIN.2.
Objectives and Endpoints
Objectives
Endpoints
Primary
To test the hypothesis that baricitinib 4-mg + TCS or 
baricitinib 2-mg + TCS is superior to placebo + TCS in 
the treatment of moderate–to-severe AD

Proportion of patients achieving EASI75 at 
Week 16
Key Secondary
These are prespecified objectives that will be adjusted for multiplicity
To test the hypothesis that baricitinib 1-mg + TCS is 
superior to placebo + TCS in the treatment of patients 
with moderate-to-severe AD

Proportion of patients achieving EASI75 at 
Week 16
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as measured by 
improvement of signs and symptoms of AD

Proportion of patients achieving IGA of 0 or 1 
with a ≥2 point improvement at 16 weeks

Proportion of patients achieving EASI90 at 
16 weeks

Percent change from baseline in EASI score at 
16 weeks

Proportion of patients achieving SCORAD75 at 
16 weeks
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as assessed by 
patient-reported outcome measures

Proportion of patients achieving a 4-point 
improvement in Itch NRS at 16, 4, 2, and 
1 weeks

Mean change from baseline in the score of 
Item 2 of the ADSS at 16 weeks and 1 week.

Mean change from baseline in Skin Pain NRS 
at 16 weeks
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as measured by 
improvement of signs and symptoms of AD

Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement from baseline at 
Week 24

Proportion of patients achieving EASI75 at 
24 weeks
Other Secondary
These are prespecified objectives that will not be adjusted for multiplicity
To test the hypothesis that baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS is 
superior to placebo + TCS in the treatment of
moderate-to-severe AD

Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at Week 4 and 
Week 52

Proportion of patients achieving EASI75 at 
Week 4 and Week 52
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as measured by 
improvement in signs and symptoms of AD

Proportion of patients achieving EASI50 at 
16 weeks

Proportion of patients achieving IGA of 0 at 
16 weeks

Mean change from baseline in SCORAD at 
16 weeks

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
Proportion of patients achieving SCORAD90 at 
16 weeks

Mean change from baseline in body surface 
area (BSA) affected at 16 weeks

Proportion of patients developing skin 
infections requiring antibiotic treatment by 
Week 16

Mean number of days without use of 
background TCS over 16 weeks

Mean gram quantity of background TCS used 
over 16 weeks (tube weights)
To compare the efficacy of baricitinib 4-mg + TCS, 
baricitinib 2-mg + TCS, or baricitinib 1-mg + TCS to 
placebo + TCS in AD during the double-blind 
placebo-controlled treatment period as assessed by 
patient-reported outcome measures

Percent change from baseline in Itch NRS at 
Weeks 52, 24, 16, 4, and 1

Proportion of patients achieving a 4-point 
improvement in Itch NRS at 24 weeks 

Mean change from baseline in the total score of 
the POEM at 16 weeks

Mean change from baseline in the PGI-S-AD 
scores at 16 weeks

Mean change from baseline in HADS total 
scores at 16 weeks

Mean change from baseline in the DLQI total 
scores at 16 weeks

Mean change from baseline in the WPAI-AD
total scores at 16 weeks

Mean change from baseline in the EQ-5D-5L 
total scores at 16 weeks
Substudy:  Randomized Downtitration
These are prespecified objectives that will be not be adjusted for multiplicity
All Patients Entering the Substudy
To evaluate the change in clinical response after 
treatment downtitration from baricitinib

4-mg to 2-mg compared with patients who are 
rerandomized to remain on baricitinib 4-mg

2-mg to 1-mg compared with patients 
randomized to remain on baricitinib 2-mg
Patients Entering the Substudy with IGA 0 or 1
To evaluate the change in clinical response after 
treatment downtitration from baricitinib

4-mg to 2-mg compared with patients who are 
rerandomized to remain on baricitinib 4-mg

2-mg to 1-mg compared with patients 
randomized to remain on baricitinib 2-mg

Proportion of patients with a response of IGA 
0, 1, or 2 assessed at 16 weeks after 
rerandomization (Week 68) and Week 104

Proportion of patients with a response of IGA 0 
or 1 assessed at 16 weeks after rerandomization
(Week 68) and Week 104

Proportion of patients with a response of 
EASI75 from baseline assessed at 16 weeks 
after rerandomization (Week 68) and Week 104

Time to retreatment (time to IGA ≥3)
Patients Not Entered into Substudy
These are prespecified objectives that will not be adjusted for multiplicity

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All Patients
1.
To evaluate the long-term effect of baricitinib 
dose on clinical measures
Patients with IGA 0 or 1
2.
To evaluate the long-term effect of baricitinib 
dose on clinical measures

Proportion of patients with a response of IGA 
0, 1, or 2 assessed at Weeks 68 and 104

Proportion of patients with a response of IGA 0 
or 1 assessed at Weeks 68 and 104

Proportion of patients with a response of 
EASI75 assessed at Weeks 68 and 104
Exploratory Endpoints 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, DLQI, WPAI-AD, EQ-5D-5L, Itch NRS, ADSS Item 1, 2, 
3 scores, Skin Pain NRS, SF-36, PGI-S-AD.  Patients continuing on placebo as responders will be assessed during 
the long-term extension for relevant efficacy endpoints. Assessments of efficacy may be performed beyond 
Week 104 up to Week 200. The timing of the data lock(s) for the analysis of the efficacy data from the randomized 
withdrawal sub-study will be determined by the retreatment rates (see Section 10.3.7).
Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; DLQI = Dermatology Life Quality 
Index; EASI = Eczema Area and Severity Index; 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; PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; POEM = Patient-Oriented 
Eczema Measure; SF-36 =Medical Outcomes Study 36-item short-form health survey; SCORAD = SCORing 
Atopic Dermatitis; TCS = topical corticosteroids; WPAI-AD = Work Productivity and Activity Impairment-
Atopic Dermatitis.

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5. Study Design
5.1.
Overall Design
Study I4V-MC-JAIN (JAIN) is a Phase 3, multicenter, double-blind, randomized, 
placebo-controlled study evaluating the safety and efficacy of baricitinib 1-mg QD, 2-mg QD,
and 4-mg QD in combination with TCS in patients with moderate-to-severe atopic dermatitis
(AD) who have experienced failure of cyclosporine, or are intolerant to, or have a 
contraindication to, cyclosporine. The study is divided into 5 periods:  a 5-week Screening 
period, a 1-year Double-Blind Treatment period (Week 0 through Week 52), a 1-year double-
blind, long-term extension (Week 52 through Week 104) that includes a randomized 
downtitration substudy, a bridging extension that may last up to 96 weeks (Week 104 to up to 
Week 200) and a 4-week Post-Treatment Follow-Up period.
Approximately 500 patients ≥18 years of age will be randomized at a 1:1:2:1 ratio to receive 
placebo QD, baricitinib 1-mg QD, baricitinib 2-mg QD, or baricitinib 4-mg QD (100 patients in 
the placebo group; 100 patients each in the baricitinib 1-mg and 4-mg groups; and 200 patients in 
the baricitinib 2-mg treatment group).  Patients will be stratified at randomization according to 
disease severity (Investigator’s Global Assessment [IGA] 3 versus 4) and geographic region if 
the planned country allocation justifies.
All procedures to be conducted during the study, including timing of all procedures, are indicated 
in the Schedule of Activities (Section 2).  Section 9.4.4 describes collection of laboratory 
samples; Appendix 2, Appendix 4, and Appendix 5 list the specific laboratory tests that will be 
performed for this study.  Study governance considerations are described in detail in Appendix 3.  
Section 10.3.7.1 outlines information regarding the data monitoring committee (DMC) and 
interim analyses.
Figure JAIN.1 illustrates the study design.

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Abbreviations:  AD = atopic dermatitis; eGFR = estimated glomerular filtration rate;
ET = early termination; IGA = Investigator’s Global Assessment; IP = investigational 
product; PPD = purified protein derivative; QD = once daily; TB = tuberculosis; TCS = 
topical corticosteroids; V = visit; W = week.
a
Applicable to patients taking topical treatments (excluding emollients) or 
systemic treatments for AD at the time of screening.
b
Maximum dose of baricitinib for patients with renal impairment (defined as 
eGFR <60 mL/min/1.73 m2) will be 2-mg QD.
c
Patients for whom PPD skin test for the evaluation of TB infection was 
performed at V1 must return and PPD test must be read 48 to 72 hours after Visit 1 
(post-PPD).
d
At Visit 2 (W0) and up to Visit 22 (W104), patients will be supplied with mild-
and moderate-potency TCS to be applied per the guidelines in Section 7.7.2.
e
At Week 52, responders (IGA 0 or 1) and partial responders (IGA 2) who were 
assigned to baricitinib 4-mg or 2-mg, at randomization, are currently receiving 
investigational product (does not currently have study drug interrupted), and have not 
used high- or ultra-high-potency TCS in the previous 14 days will be enrolled into the 
downtitration substudy. If a patient in the substudy has an IGA ≥3 during Periods 3 or 
4, they will be retreated automatically with their presubstudy baricitinib dose for the 
remainder of the study.

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f
At Week 52, responders (IGA 0 or 1) and partial responders (IGA 2) in the 
baricitinib 4-mg or baricitinib 2-mg treatment groups who are not eligible for the 
randomized downtitration substudy and those who are in the baricitinib 1-mg or 
placebo groups will remain on their current dose of investigational product.  If 
worsening of AD symptoms occurs any time during Periods 3 or 4 such that a patient’s 
IGA is ≥3, with the exception of patients in the baricitinib 4-mg group, they will be 
rerandomized automatically at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 4-mg 
QD.  Rerandomization will only occur once. Patients in the baricitinib 4-mg group will 
remain on 4-mg.
g
Beginning at Visit 14 (Week 52), nonresponders (IGA ≥3) in the placebo, 
baricitinib 1-mg or baricitinib 2-mg treatment groups will be rerandomized at a 1:1 
ratio to baricitinib 4-mg or baricitinib 2-mg QD. Nonresponders randomized to 
baricitinib 4-mg at baseline will remain on 4-mg.  After rerandomization, patients will 
remain on the same dose of baricitinib for the remainder of the study.
h
Occurs approximately 28 days after the last dose of IP. Not required for patients 
who have been off drug for 28 days or more at the time of their last visit. 
Figure JAIN.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIN.
5.1.1. Period 1:  Screening and Baseline Period
The duration of the Screening Period is between 8 and 35 days prior to Visit 2 (Week 0).  At 
Visit 1, the patient will sign the informed consent form (ICF) prior to any study assessments, 
examinations, or procedures being performed (see Appendix 3). All screening procedures will 
be performed according to the Schedule of Activities (Section 2). Patients who receive a purified 
protein derivative (PPD) skin test at Visit 1 will need to return within 48 to 72 hours later to read 
the skin test. Prior to randomization, treatments for AD will be washed out: 5 half-lives for 
biologic treatments, 4 weeks for systemic treatments, and 2 weeks for topical treatments (not 
including emollients). Patients will be required to use emollients daily during the 14 days 
preceding randomization and throughout the study. On study visit days, patients are requested 
not to apply emollients until after the assessments are completed.  If patients have been using 
emollients daily at the time of screening, then those cumulative days can be utilized to meet
inclusion criterion [9]. Additionally, collection of data through daily diaries will be required 
throughout the screening period. The baseline for the daily PRO assessments will be the average 
score of the 7 days prior to randomization; thus the minimum screening window was set at 
8 days.
All eligible patients who have not previously received the herpes zoster vaccine by screening 
will be encouraged (per local guidelines) to do so prior to randomization. Refer to the exclusion 
criterion [29] in Section 6 for additional information regarding herpes zoster vaccinations.  
Investigators should review the vaccination status of their patients and follow the local 
guidelines for vaccination of those ≥18 years of age with nonlive vaccines intended to prevent 
infectious disease prior to entering patients into the study.  
Patients who meet all of the inclusion and none of the exclusion criteria (Section 6) will continue 
to Visit 2.

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5.1.2. Period 2:  Double-Blind Placebo-Controlled Treatment
At Visit 2 (Week 0, baseline), study eligibility for each patient will be reviewed, based on all 
inclusion and exclusion criteria (Section 6), and laboratory test results.  Patients who meet all 
criteria will proceed to randomization and begin the 52-week double-blind, placebo-controlled
treatment period.
At Visit 2, laboratory samples will be collected and all assessments should be completed before 
the patient takes the first dose of investigational product.  The first dose of investigational 
product should be administered on-site.
Patients will be randomized at a 1:1:2:1 ratio to 1 of 4 treatment groups (placebo QD, baricitinib 
1-mg QD, baricitinib 2-mg QD, or baricitinib 4-mg QD). Patients will also apply background 
TCS therapy (e.g., triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment) on active 
lesions, as described in Section 7.7.2 (Use of Topical Corticosteroids). Use of TCIs and/or 
crisaborole (where approved) will be permitted as background therapy on areas where 
application of TCS is considered inappropriate by investigator (e.g., face, neck, skin folds, 
genital areas; see Section 7.7.1 [Permitted Medications and Procedures]).  High- or ultra-high 
potency TCS (Class I to III; see Appendix 7) and all systemic therapies used for treating AD will
not be allowed, unless used as directed as part of rescue therapy (see guidelines in Section 7.7.5
[Rescue Therapy]) and only at the discretion of the investigator. Rescue to baricitinib will not 
occur during treatment Period 2.
Assessments of disease severity will be performed by the investigator at all study visits including 
unscheduled and early termination visits (ETVs).  On study visit days, patients are requested not 
to apply emollients nor TCS until after the assessments are completed. Daily diary collection will 
continue through all 52 weeks of treatment in Period 2 of JAIN.
The primary efficacy endpoint will be at Week 16 (Visit 8).  All patients who permanently 
discontinue investigational product prior to the primary endpoint, including patients rescued with
other systemic medications, should remain in the study to complete the schedule of study visits 
per protocol up to Week 16 (primary endpoint), when they will complete an ETV.  If the patient 
refuses to continue up to Week 16 and wishes to withdraw consent, an ETV should be completed 
as soon as logistically possible.
5.1.3. Period 3:  Double-Blind, Long-Term Extension
Patients who complete the study through Week 52 will progress into the double-blind long-term 
extension phase through Week 104 (Visit 22). Daily diary collection will continue through 
Week 68 (Visit 18) of Period 3.
Concomitant use of background TCS therapy will continue during this treatment period as 
described in Section 7.7.2.
5.1.3.1.
Randomized Downtitration Substudy at Week 52
At Week 52, all patients will be evaluated for substudy eligibility. To be eligible, a patient must
meet all of the following criteria:

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
have an IGA 0, 1 (Responder) or 2 (Partial responder) at Week 52

have not used high- or ultra-high potency TCS in the last 14 days (potency 
classification in Appendix 7)

do not currently have study drug interrupted

have been assigned to baricitinib 2-mg or 4-mg at baseline (assessed by interactive 
web-response system [IWRS])
Treatment
Treatment in the substudy is illustrated in Figure JAIN.1. Patients eligible for the substudy will 
be rerandomized at a 1:1 ratio at Week 52 based on the baricitinib treatment group assigned at 
baseline:

4-mg QD rerandomized to baricitinib 4-mg QD, or baricitinib 2-mg QD

2-mg QD rerandomized to baricitinib 2-mg QD, or baricitinib 1-mg QD
Note:  Intensification of emollients and TCS may be continued or initiated to control worsening 
and unacceptable symptoms of AD any time during this treatment period. For management of 
TCS, follow the guidelines in Section 7.7.2.
Retreatment
During the substudy, if worsening of AD symptoms occurs such that IGA increases to ≥3, the 
patient will be automatically retreated with their presubstudy baricitinib dose.  When the IGA is 
≥3, the investigator should reinitiate background TCS therapy (e.g., triamcinolone 0.1% cream 
and/or hydrocortisone 2.5% ointment), provided the patients are not currently using TCS, and 
may prescribe high- or ultra-high-potency TCS following the guidelines for use of Rescue 
Therapies (Section 7.7.5 [Rescue Therapy]). An unscheduled visit may be needed to assess 
worsening of symptoms and to perform clinical safety and efficacy assessments immediately 
before retreatment.
Investigators will be aware of the patients not meeting the first 3 eligibility criteria for 
randomized downtitration substudy; however, they will not be aware of the patient’s dose
assigned at randomization. As such, IGA ≥3 will be the criterion for both retreatment (in the 
substudy) and rescue for patients not eligible for the substudy, as described below, to ensure that 
all patients are treated similarly and that the blinding to treatment group is preserved. In 
addition, all patients, regardless of whether entered into the substudy or not, will follow all study
procedures in Period 3 to maintain the blind.
5.1.3.2.
Patients Not Eligible for the Substudy
Beginning at Week 52,

Patients with an IGA ≥3 who
o
are in the baricitinib 2-mg, 1-mg, and placebo treatment groups will be 
automatically rerandomized at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 
4-mg QD.

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o
are in the baricitinib 4-mg treatment group will remain on 4-mg QD (see “Rescue 
during Period 3” Section 7.7.5.2).

Patients with an IGA 0, 1, or 2 who
o
are in the baricitinib 4-mg or 2-mg treatment groups and who are not eligible for 
the substudy (i.e., have study drug interrupted at Week 52, or have received high-
or ultra-high potency TCS in the previous 14 days), or are in the placebo or 
baricitinib 1-mg groups will continue in their current treatment group.
o
Patients who experience a worsening of symptoms of AD such that IGA increases 
to ≥3 will be rerandomized at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 
4-mg QD.  Patients in the baricitinib 4-mg group will remain on 4-mg.
This option for rescue is only available once for each patient and will be assigned by IWRS; 
investigators will remain blinded to treatment assignments. The investigator may reinitiate 
background TCS therapy (e.g., triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment), 
provided the patients are not currently using TCS, and may prescribe high- or ultra-high-potency 
TCS following the guidelines for use of rescue therapies (see Section 7.7.5).
Once a patient has an IGA ≥3 in Period 3, the investigator will know that a patient is on the 
highest dose of baricitinib that he/she will receive in the study; therefore, if AD symptoms 
remain unacceptable then discontinuation should be considered.
5.1.4. Period 4: Bridging Extension
Patients who have completed Week 104 and have not met criteria for permanent discontinuation 
will have the possibility to remain in the trial for up to 96 additional weeks (up to Week 200).
During Period 4, patients will continue to receive the same treatment (baricitinib or placebo) they 
received during Period 3, and will have the same options for dose changes as Period 3 (if not 
already implemented in Period 3):

Randomized Down titration substudy: the substudy will continue during Period 4. 
Therefore, patients who have not met the criterion for retreatment in Period 3 will have 
the possibility to be retreated with the baricitinib dose they received prior to the substudy 
if worsening of AD symptoms occurs such that IGA increases to ≥3. 

Patients with an IGA 0, 1, or 2 at Week 52 and who were not eligible to the randomized 
downtitration, will be rerandomized at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 
4-mg QD if they experience a worsening of symptoms of AD such that IGA increases to
≥3, unless the randomized uptitration has already occurred in Period 3. Patients in the 
baricitinib 4-mg group will remain on 4-mg. 
5.1.5. Period 5:  Post-Treatment Follow-Up
Patients who complete the study through 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 must 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.

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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 chose to discontinue early; 
however, a separate follow-up visit (Visit 801) is not required.
If a patient permanently discontinues investigational product for any reason before Week 16 
(Visit 8), the patient is encouraged to remain in the study through Week 16 (Visit 8) and follow 
the regular visit schedule to provide the primary efficacy and safety data (See Section 5.1.3).
5.2.
Number of Participants
Approximately 500 participants will be enrolled; approximately 714 patients will be screened to
achieve this enrollment.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
This study will enroll patients with moderate-to-severe AD who have a history of failure to 
cyclosporine or who are intolerant to, or have contraindication to, cyclosporine, for whom a 
systemic treatment such as baricitinib may therefore be appropriate.
Topical corticosteroids are the first-line anti-inflammatory treatment, even for patients treated 
with systemic treatments. For this reason, this study will assess the efficacy of baricitinib in 
combination with background mild- to moderate-potency TCS, used as determined appropriate 
by the investigator.
Both EASI score and Investigator’s Global Assessments are commonly used in clinical trials, 
both for qualifying patients for enrollment and for evaluating treatment efficacy (Langley et al. 
2015; Futamura et al. 2016; Bożek and Reich, 2017). There is no single “gold standard” disease 
severity scale for AD; however, IGA scales provide clinically meaningful measures to patients 
and investigators that are easily described and that correspond to disease severity categories (for 
example, moderate to severe) and a 75% improvement from Baseline (EASI75) is a commonly 
used measure of treatment effect in AD clinical trials. The IGA scale that will be used in this 
trial, the validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD, referred 
to throughout the protocol as IGA) assesses AD severity using a 5-point scale (0 to 4).  It was
developed in partnership with a multi-stakeholder consortium, including experts in AD, industry 
partners, and academia.  Development of the vIGA-AD also included the development of a 
training video and certification exam to ensure consistency across raters. The scale and all 
training materials are available to all other pharmaceutical companies, as well as any academic 
investigator interested in using the scale through the International Eczema Council.
During the screening period (Period 1), a washout of systemic and topical treatments for AD is
incorporated prior to randomization to minimize confounding effects due to background 
treatment.

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The 52-week double-blind, placebo-controlled treatment period (Period 2) is designed to 
evaluate the efficacy and safety of 3 doses of baricitinib relative to placebo, in combination with 
TCS, both in short-term and long-term treatment of patients with moderate-to-severe AD.  Study 
JAIN will include the possibility to downtitrate baricitinib in patients who are responders (IGA 0 
or 1) or partial responders (IGA 2) in the context of a randomized downtitration substudy starting 
at Week 52.  Study JAIN will also evaluate the possibility to uptitrate nonresponders (IGA ≥3) 
during Period 3.
A 1:1:2:1 randomization scheme of placebo, 1-mg baricitinib, 2-mg baricitinib, and 4-mg 
baricitinib was implemented in JAIN to obtain additional efficacy and safety data for the 2-mg 
dose of baricitinib relative to other studies conducted with baricitinib in AD.
All patients in Study JAIN will be assigned investigational product with concomitant mild- to 
moderate-potency TCS until Week 104 (Visit 22) and investigators may rescue patients who are 
experiencing unacceptable or worsening symptoms of AD with high- or ultra-high-potency TCS.  
(See Section 7.7.5 for all rescue options). 
Topical rescue treatments (as outlined in Section 7.7.5) will be available during Study JAIN to 
facilitate the management of disease, as there are instances where patients will remain on the 
same dose of baricitinib during episodes of worsening.
The 16-week efficacy endpoint was chosen because it is likely that a robust clinical effect will be 
observed with baricitinib within this timeframe based on the Phase 2 study results in AD, and for 
consistency with other studies in AD. This timing will allow adequate duration on a stable dose 
of baricitinib to assess the benefit/risk profile of the dose regimens.
During the long-term extension (Period 3), eligible patients will participate in a downtitration 
substudy.  The objective of the substudy is to evaluate the possibility of maintaining efficacy 
with a lower dose of baricitinib in patients with response (IGA 0 or 1) or partial response 
(IGA 2) to baricitinib 2-mg QD or 4-mg QD in combination with TCS.
Period 4 will provide patients who have completed Week 104 visit and have not met criteria for 
permanent discontinuation, the possibility to remain in the trial for up to 96 additional weeks (up 
to Week 200). This will allow for additional long-term efficacy and safety information to be 
collected, and provide patients the opportunity to continue study treatment until the anticipated 
approval of baricitinib in this indication.
The Post-Treatment Follow-Up Period (Period 5) is for safety monitoring after the patient has 
been off investigational product for approximately 28 days.
5.5.
Justification for Dose
The doses proposed for AD Phase 3 studies are baricitinib 1-mg, 2-mg, and 4-mg QD.  These 
doses were chosen primarily based on the recently completed Phase 2 AD study, JAHG, and are 
additionally supported by pharmacokinetic (PK), safety, and efficacy data for baricitinib in 
Phase 2 and Phase 3 RA studies and a Phase 2 psoriasis study.

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In the Phase 2 Study JAHG, both the 2-mg and 4-mg doses showed benefit on the primary and 
major secondary endpoints (EASI, IGA, SCORing Atopic Dermatitis [SCORAD], 
Patient-Oriented Eczema Measure [POEM], and Dermatology Life Quality Index [DLQI]) as 
compared to placebo, and both doses had an acceptable safety profile at Week 16.
The 4-mg dose appeared to demonstrate a more rapid benefit (at 4 weeks) on the more stringent 
endpoints (EASI75, EASI90, and IGA 0 or 1) compared to 2-mg dose particularly in the 
subgroup of patients with baseline EASI scores ≥16.  The 4-mg dose resulted in statistically 
significant improvement in these endpoints at Week 4 and this level of response was maintained 
through Week 16.  Additionally, statistical significance for EASI75 for the 4-mg dose compared 
to placebo also occurred at Week 4, and this level of response was maintained through Week 16.  
A similar trend between the baricitinib 4-mg and 2-mg doses was observed in patients with RA.  
However, on other endpoints including EASI50, and EASI change from baseline, 2-mg and 4-mg 
doses show similar efficacy compared to placebo. Thus, based on available data, 3 doses will be 
included in Phase 3, including a 1-mg dose, to cover the range of exposures where clinical 
responses could be anticipated.
5.5.1. Rationale for Dose Adjustment for Renal Impairment
Baricitinib exposure increases with decreased renal function. Based on PK simulations of 
baricitinib exposures for the mild and moderate categories of renal function (stratified as 
estimated glomerular filtration rate [eGFR] 60 to <90 mL/min/1.73 m2 and eGFR 30 to 
<60 mL/min/1.73 m2, respectively), dose adjustment is not required for patients with 
eGFR ≥60 mL/min/1.73 m2. Patients with eGFR <60 mL/min/1.73 m2 who are randomized to 
the 4-mg dose will receive a dose of 2–mg QD, which will ensure that exposures do not exceed 
those of the 4-mg QD dose in patients with eGFR ≥60 mL/min/1.73 m2. For patients randomized 
to the 2-mg dose or 1-mg dose, there will be no dose adjustment based on renal function.  The 
dose adjustment for renal impairment will be managed by IWRS to ensure maintenance of the 
treatment blind.  This study will not enroll patients with screening eGFR <40 mL/min/1.73 m2. 
See Section 8.1.1 for eGFR thresholds that trigger interruption of investigational product.
The procedure for dose adjustment based on renal function (eGFR) during the study is detailed in 
Section 7.2.2.

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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
Study investigator(s) will review patient history and screening test results at Visit 1 and Visit 2 to 
determine if the patient meets all inclusion and none of the exclusion criteria to qualify for
randomization in the study. All screening activities must be completed and reviewed before the
patient is randomized.
6.1.
Inclusion Criteria
Informed consent
[1]
are at least 18 years of age at the time of informed consent
Note:  Use local requirements to provide consent if the age of adulthood is 
defined as >18 years
[2]
are able to read, understand, and give documented (electronic or paper 
signature) informed consent.
Type of Patient and Disease Characteristics
[3]
have a diagnosis of AD at least 12 months prior to screening, as defined by the 
American Academy of Dermatology: Guidelines of care for the management 
of AD; Section 1.  Diagnosis and assessment of atopic dermatitis (see 
Appendix 6).
[4]
have moderate-to-severe AD, including all of the following:
a.
EASI score ≥16 at Screening (Visit 1) and at randomization (Visit 2)
b. IGA score of ≥3 at Screening (Visit 1) and at randomization (Visit 2)
c.
≥10% of BSA involvement at Screening (Visit 1) and at randomization 
(Visit 2)
[5]
have a history documented by a physician and/or investigator of an inadequate 
response to existing topical medications within 6 months preceding screening, 
defined as: inability to achieve good disease control (e.g., not able to achieve 
IGA ≤2) after use of at least a moderate-potency TCS for at least 4 weeks, or 
for the maximum duration recommended by the product prescribing 
information (e.g., 14 days for ultra-high-potency TCS), whichever is shorter.
[6]
have a history documented by a physician and/or investigator of either:
a.
medical contraindications to cyclosporine:

Hypersensitivity to the active substance or to any of the excipients

Medical conditions (e.g., uncontrolled hypertension on medication)

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
Use of prohibited concomitant medications: products containing 
hypericum perforatorum (St John’s Wort), medicines that are 
substrates of CYP3A4, multidrug efflux transporter P-glycoprotein and 
organic anion transporter proteins (OATP):  bosentan, dabigatran 
etexilate, aliskiren, statins, angiotensin-converting-enzyme inhibitors, 
lercanidipine, etc.

Increased susceptibility to cyclosporine-induced renal damage 
(elevated creatinine) and liver damage (elevated function tests), or 
increased risk of serious infections.
b. intolerance and/or unacceptable toxicity to cyclosporine (e.g., elevated 
creatinine, elevated liver function tests, uncontrolled hypertension, 
paresthesia, headache, nausea, hypertrichosis, etc.), or
c.
Inadequate response to cyclosporine (CyA) defined as failure to obtain 
good disease control (i.e., remission or low disease activity) within 
6 weeks of treatment with CyA dosed at 2.5 to 5 mg/kg/day, or 
requirement for CyA at doses >5 mg/kg/day, or for a duration beyond that 
specified in the prescribing information (>1 year).
[7]
agree to discontinue use of the following excluded medications/treatments for 
at least 4 weeks prior to randomization (Visit 2) and throughout the study 
unless otherwise specified below:
a.
oral systemic corticosteroids
b. systemic immunomodulators, including but not limited to cyclosporine, 
methotrexate, mycophenolate mofetil, and azathioprine
c.
sedating systemic antihistamines, including but not limited to 
alimemazine, chlorphenamine, clemastine, cyproheptadine, 
diphenhydramine, hydroxyzine, ketotifen, and promethazine during 
Periods 1 and 2.  Sedating antihistamines may be used during Period 3.
Note: Patients may use newer, less-sedating antihistamines (e.g., 
fexofenadine, loratadine, cetirizine) throughout the trial.
d. any other systemic therapy used to treat AD or symptoms of AD
(approved or off-label use)
e.
phototherapy, including therapeutic phototherapy (psoralen plus 
ultraviolet A, ultraviolet B, excimer laser) as well as self-treatment with 
tanning beds.
[8]
agree to discontinue use of the following excluded medications for at least 
2 weeks prior to randomization (Visit 2):
a.
topical corticosteroids (TCS) or topical immune modulators (e.g., 
tacrolimus or pimecrolimus).  Note:  Mild- and moderate-potency TCS 
will be administered as concomitant therapy for all patients, beginning at 
Visit 2; refer to Section 7.7.1 and 7.7.2 for further information.

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b. topical phosphodiesterase type 4 (PDE-4) inhibitor (crisaborole)
[9]
have applied emollients daily for at least 14 days prior to randomization and 
agree to use emollient daily throughout the treatment period
[10]
Patients who are receiving chronic treatments to improve sleep should be on a 
stable dose for at least 2 weeks prior to screening as determined by the 
investigator. Sedating antihistamines (see above) are not permitted.
Patient Characteristics
[11]
are male or nonpregnant, nonbreastfeeding female patients, except
a.
Male patients will either remain abstinent (if this is their preferred and 
usual lifestyle) or agree to use 2 forms of birth control (one 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.
b. Female patients of child-bearing potential who are abstinent (if this is 
complete abstinence, as their preferred and usual lifestyle) or in a same-
sex relationship (as part of their preferred and usual lifestyle) must agree 
to either remain abstinent or stay in a same-sex relationship without sexual 
relationships with males. Periodic abstinence (e.g., 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):

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 (e.g., progestin-releasing 
coil); or, vasectomized male (with appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate).

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.

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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 
and they are defined as:

women ≥60 years of age or women who are congenitally sterile, or

women ≥40 and <60 years of age who have had a cessation of menses 
for ≥12 months and a follicle-stimulating hormone (FSH) test 
confirming nonchildbearing potential (≥40 mIU/mL or ≥40 IU/L), or 
women who are surgically sterile (i.e., 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:
Medical Conditions Related to Atopic Dermatitis
[12]
are currently experiencing or have a history of other concomitant skin 
conditions (e.g., psoriasis or lupus erythematosus) that would interfere with 
evaluations of the effect of study medication on AD
[13]
have had an important side effect to TCS (e.g., intolerance to treatment, 
hypersensitivity reactions, significant skin atrophy, systemic effects), as 
assessed by the investigator or treating physician that would prevent further 
use.
[14]
patients who, in the opinion of the investigator, are currently experiencing or 
have a history of erythrodermic, refractory, or unstable skin disease that 
requires frequent hospitalizations and/or IV treatment for skin infections that 
may interfere with participation in the study
[15]
a history of eczema herpeticum within 12 months prior to screening
[16]
a history of 2 or more episodes of eczema herpeticum in the past
[17]
patients who are currently experiencing a skin infection that requires treatment 
or is currently being treated with topical or systemic antibiotics
Note:  Patients may be rescreened at least 4 weeks after the date of their 
previous screen failure and at least 2 weeks after resolution of the infection.
[18]
have any serious concomitant illness that is anticipated to require the use of 
systemic corticosteroids or otherwise interfere with study participation or 
require active frequent monitoring (e.g., unstable chronic asthma)
[19]
have been treated with the following therapies:
a.
monoclonal antibody (e.g., ustekinumab, omalizumab, dupilumab) less 
than 5 half-lives prior to randomization

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b. any oral JAK inhibitor (e.g., tofacitinib, ruxolitinib) less than 4 weeks 
prior to randomization
c.
any parenteral corticosteroid administered by intramuscular or IV injection 
within 2 weeks prior to study entry (Visit 1) or within 6 weeks prior to 
planned randomization (Visit 2) or are anticipated to require parenteral 
injection of corticosteroids during the study
d. intraarticular corticosteroid injection within 2 weeks prior to study entry 
(Visit 1) or within 6 weeks prior to planned randomization (Visit 2)
Note:  Intranasal or inhaled steroid use is allowed throughout Study JAIN.
e.
probenecid at the time of the randomization (Visit 2) that cannot be 
discontinued for the duration of the study
Medical Conditions in General
[20]
are largely or wholly incapacitated permitting little or no self-care, such as 
being bedridden
[21]
have uncontrolled arterial hypertension characterized by a repeated systolic 
blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg in a 
seated position
[22]
have had any major surgery within 8 weeks prior to screening or will require 
major surgery during the study that, in the opinion of the investigator in 
consultation with Eli Lilly and Company (Lilly) or its designee, would pose an 
unacceptable risk to the patient if he or she is participating in the trial.
[23]
are immunocompromised and, in the opinion of the investigator, at an 
unacceptable risk for participating in the study
[24]
have experienced any of the following within 12 weeks of screening:  venous 
thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic 
heart disease, stroke, or New York Heart Association Stage III/IV heart failure
[25]
have a history of recurrent (≥2) VTE or are considered at high risk of VTE as 
deemed by the investigator
[26]
have a history or presence of cardiovascular, respiratory, hepatic, 
gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric 
disorders or any other serious and/or unstable illness that, in the opinion of the 
investigator, could constitute an unacceptable risk when taking investigational 
product or interfere with the interpretation of data.
[27]
have a history of lymphoproliferative disease; or have signs or symptoms 
suggestive of possible lymphoproliferative disease, including 
lymphadenopathy or splenomegaly; or have active primary or recurrent 
malignant disease; or have been in remission from clinically significant 
malignancy for less than 5 years.

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a.
Patients with cervical carcinoma in situ that has been appropriately treated
with no evidence of recurrence or metastatic disease for at least 3 years 
may participate in the study.
b. Patients with basal cell or squamous epithelial skin cancers that have been 
appropriately treated with no evidence of recurrence for at least 3 years 
may participate in the study.
[28]
have a current or recent and/or serious viral, bacterial, fungal, or parasitic 
infection, including but not limited to the following:
a.
symptomatic herpes zoster infection within 12 weeks prior to screening
b. a history of disseminated/complicated herpes zoster (e.g., 
multidermatomal involvement, ophthalmic zoster, central nervous system 
involvement, or post-herpetic neuralgia)
c.
symptomatic herpes simplex at the time of randomization
d. active or chronic viral infection from hepatitis B virus (HBV), hepatitis C 
virus (HCV), or human immunodeficiency virus (HIV)
e.
household contact with a person with active tuberculosis (TB) and did not 
receive appropriate and documented prophylaxis for TB
f.
evidence of active TB or have previously had evidence of active TB and 
did not receive appropriate and documented treatment
g. clinically serious infection or received IV antibiotics for an infection, 
within the past 4 weeks of randomization
Note:  A recent viral upper respiratory tract infection or uncomplicated 
urinary tract infection should not be considered clinically serious.
h. any other active or recent infection within 4 weeks of randomization that, 
in the opinion of the investigator, would pose an unacceptable risk to the 
patient if participating in the study
[29]
have been exposed to a live vaccine within 12 weeks prior to planned 
randomization or are expected to need/receive a live vaccine during the course 
of the study (with the exception of herpes zoster vaccination).
Note: Patients eligible for herpes zoster vaccine (as per local guidelines) who 
have not received it prior to screening will be encouraged to do so prior to 
randomization; vaccination must occur >4 weeks prior to randomization and 
start of investigational product.  Patients will be excluded if they were exposed 
to herpes zoster vaccination within 4 weeks of planned randomization.
[30]
have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug 
abuse within the 2 years prior to screening

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[31]
presence of significant uncontrolled neuropsychiatric disorder, are clinically 
judged by the investigator to be at risk for suicide, or have a “yes” answer to 
any of the following:
a.
Question 4 (Active Suicidal Ideation with Some Intent to Act, Without 
Specific Plan) on the “Suicidal Ideation” portion of the Columbia Suicide 
Severity Rating Scale (C-SSRS) or
b. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the 
“Suicidal Ideation” portion of the C-SSRS or
c.
Any of the suicide-related behaviors (actual attempt, interrupted attempt, 
aborted attempt, preparatory act or behavior) on the “Suicidal Behavior” 
portion of the C-SSRS
And the ideation or behavior occurred within 2 months prior to Visit 1.
Note: A patient does not necessarily have to be excluded if they have 
self-injurious behavior that would be classified as nonsuicidal self-injurious 
behavior.  Of course, if this situation arises, it is likely the subject should be 
referred to a psychiatrist or appropriately trained professional.
[32]
have donated more than a single unit of blood within 4 weeks prior to 
screening or intend to donate blood during the course of the study
Other Exclusions
[33]
are unable or unwilling to make themselves available for the duration of the 
study and/or are unwilling to follow study restrictions/procedures, including 
use of data collection devices
[34]
are currently enrolled in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study
[35]
have participated, within the last 30 days in a clinical study involving an 
investigational product.  If the previous investigational product has a long 
half-life (2 weeks or longer), at least 3 months or 5 half-lives (whichever is 
longer) should have passed.
[36]
have previously been randomized in this study or any other study investigating 
baricitinib
[37]
are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, regardless of whether biological or legally adopted
[38]
are Lilly or Incyte employees or their designee

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Diagnostic Assessments
[39]
have screening electrocardiogram (ECG) abnormalities that, in the opinion of 
the investigator, are clinically significant and indicate an unacceptable risk for 
the patient’s participation in the study
[40]
have evidence of active TB or latent TB
a.
have evidence of active TB, defined in this study as the following:

documented by a positive PPD test (≥5 mm induration between 
approximately 48 and 72 hours after application, regardless of 
vaccination history), medical history, clinical features, and abnormal 
chest x-ray at screening.

The QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available 
and if compliant with local TB guidelines) may be used instead of the 
PPD test.  Patients are excluded from the study if the test is not 
negative and there is clinical evidence of active TB.
Exception: Patients with a history of active TB who have documented 
evidence of appropriate treatment, have no history of re-exposure since their 
treatment was completed, and have a screening chest x-ray with no evidence of 
active TB may be enrolled if other entry criteria are met.  Such patients would 
not be required to undergo the protocol-specific TB testing for PPD, 
QuantiFERON®-TB Gold test, or T-SPOT®.TB test but must have a chest 
x-ray at screening.
b. Have evidence of untreated/inadequately or inappropriately treated latent 
TB, defined in this study as the following:

documented to have a positive PPD test (≥5 mm induration between 
approximately 48 and 72 hours after application, regardless of 
vaccination history), no clinical features consistent with active TB, and 
a chest x-ray with no evidence of active TB at screening; or

PPD test is positive and the patient has no medical history or chest 
x-ray findings consistent with active TB, the patient may have a 
QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if 
compliant with local TB guidelines).  If the test results are not 
negative, the patient will be considered to have latent TB (for purposes 
of this study); or 

QuantiFERON®-TB Gold test or T-SPOT®.TB test (as available and if 
compliant with local TB guidelines) may be used instead of the PPD 
test.  If the test results are positive, the patient will be considered to 
have latent TB.  If the test is not negative, the test may be repeated 
once within approximately 2 weeks of the initial value.  If the repeat 
test results are again not negative, the patient will be considered to 
have latent TB (for purposes of this study).

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Exception:  Patients who have evidence of latent TB may be enrolled if he or 
she completes at least 4 weeks of appropriate treatment prior to randomization 
and agrees to complete the remainder of treatment while in the trial.
Exception:  Patients with a history of latent TB who have documented 
evidence of appropriate treatment, have no history of re-exposure since their 
treatment was completed, and have a screening chest x-ray with no evidence of 
active TB may be enrolled if other entry criteria are met.  Such patients would 
not be required to undergo the protocol-specific TB testing for PPD, 
QuantiFERON®-TB Gold test, or T-SPOT®.TB test but must have a chest 
x-ray at screening.
[41]
have a positive test HBV infection defined as:
a.
positive for hepatitis B surface antigen (HBsAg), or 
b. positive for hepatitis B core antibody (HBcAb) and positive HBV DNA
Note: Patients who are HBcAb positive and HBV DNA negative may be 
enrolled in the study. Patients who meet these criteria at screening will be 
identified by the central laboratory and monitored during the study.
[42]
have HCV infection (positive for anti-hepatitis C antibody with confirmed 
presence of HCV RNA)
Note: Patients who have documented anti-HCV treatment for a past HCV 
infection AND are HCV RNA negative may be enrolled in the study.
[43]
have evidence of HIV infection and/or positive HIV antibodies
[44]
have screening laboratory test values, including thyroid-stimulating hormone 
(TSH), outside the reference range for the population or investigative site that, 
in the opinion of the investigator, pose an unacceptable risk for the patient’s 
participation in the study
Note: Patients who are receiving thyroxine as replacement therapy may 
participate in the study, provided stable therapy has been administered for 
≥12 weeks and TSH is within the laboratory’s reference range.  Patients who 
have TSH marginally outside the laboratory’s normal reference range and are 
receiving stable thyroxine replacement therapy may participate if the treating 
physician has documented that the thyroxine replacement therapy is adequate 
for the patient.
[45]
have any of the following specific abnormalities on screening laboratory tests:
a.
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2x 
the upper limit of normal (ULN)
b. alkaline phosphatase (ALP) ≥2 x ULN
c.
total bilirubin ≥1.5x the ULN
d. hemoglobin <10.0 g/dL (100.0 g/L)

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e.
total white blood cell count <2500 cells/L(<2.50x103/L or <2.50 GI/L)
f.
neutropenia (absolute neutrophil count [ANC] <1200 cells/L) 
(<1.20x103/L or <1.20 GI/L)
g. lymphopenia (lymphocyte count <750 cells/L) (<0.75x103/L or 
<0.75 GI/L)
h. thrombocytopenia (platelets <100,000/L) (<100x103/L or <100 GI/L)
i.
eGFR <40 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology 
Collaboration [CKD-EPI] Creatinine 2009 equation)
Note:  For cases with any of the aforementioned laboratory abnormalities (Exclusion Criteria
[44] and [45]), the tests may be repeated during screening, and values resulting from repeat 
testing may be accepted for enrollment eligibility if they meet the eligibility criterion.
6.3.
Lifestyle Restrictions
Not applicable.
6.4.
Screen Failures
Patients who are entered into the study but do not meet the enrollment criteria for participation in 
this study (screen failure) may be rescreened a maximum of 2 times.  The interval between 
screen failure and rescreenings should be at least 4 weeks.  At the time of rescreening, the 
individual must sign a new ICF, repeat all necessary screening procedures, and will be assigned a 
new identification number.
If a patient undergoes rescreening, radiographic images acquired as part of initial screening and 
within 6 months of randomization may be used.

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7. Treatments
7.1.
Treatments Administered
This study involves a comparison of placebo, baricitinib 1-mg, baricitinib 2-mg, and baricitinib 
4-mg administered orally once a day. Table JAIN.3 shows the treatment regimens.
Table JAIN.3.
Treatment Regimens
Regimen
Investigational Product Supplied
Dose
Baricitinib 4-mg QDa
Baricitinib 4-mg tablets
3 tablets per day
Placebo to match 2-mg tablets
Placebo to match 1-mg tablets
Baricitinib 2-mg QD
Baricitinib 2-mg tablets
3 tablets per day
Placebo to match 4-mg tablets
Placebo to match 1-mg tablets
Baricitinib 1-mg QD
Baricitinib 1-mg tablets
3 tablets per day
Placebo to match 4-mg tablets
Placebo to match 2-mg tablets
Placebo QD
Placebo to match 4-mg tablets
3 tablets per day
Placebo to match 2-mg tablets
Placebo to match 1-mg tablets
Abbreviation:  QD = once daily.
a
The baricitinib dose for patients randomized to the 4-mg QD treatment group who have renal impairment 
(defined as eGFR <60 mL/min/1.73 m2) will be 2-mg QD.
The investigator or his/her designee is responsible for the following:

explaining the correct use of the investigational agent(s) to the patient

verifying that instructions are followed properly

maintaining accurate records of investigational product dispensing and collection

at the end of the study returning all unused medication to Lilly, or its designee, unless the 
sponsor and sites have agreed 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 products:

tablets containing 4-mg of baricitinib

tablets containing 2-mg of baricitinib

tablets containing 1-mg of baricitinib

placebo tablets to match baricitinib 4-mg tablets, 2-mg tablets, and 1-mg tablets.
Packaging for each dose will include 3 tablets per day. Each tablet has a distinctive shape and
color, 4-mg versus 2-mg versus 1-mg, and each strength tablet has a matching placebo. Each 

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active dose package will contain the appropriate active strength tablet, and corresponding 
placebo tablets for the other strengths, as noted in Table JAIN.3.
Investigational product tablets will be provided in blister packs.
Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized in a 1:1:2:1 ratio to receive 
placebo QD, baricitinib 1-mg QD, 2-mg QD, or 4-mg QD to double-blind treatment at Visit 2
(Week 0).  Randomization will be stratified by geographic region if the planned country 
allocation justifies, and disease severity at baseline (IGA 3 versus 4). Assignment to treatment 
groups will be determined by a computer-generated random sequence using an IWRS.  The 
IWRS will be used to assign cartons, each containing 4 blister packs of double-blind 
investigational product tablets to each patient, starting at Visit 2 (Week 0), and at each visit up to 
and including Visit 28 (Week 200).  Site personnel will confirm that they have located the 
correct carton by entering a confirmation number found on the carton into the IWRS.
7.2.1. Selection and Timing of Doses
The investigational product (3 tablets from blister pack) 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.
7.2.2. Dose Adjustment for Renal Impairment
The rationale of dose adjustment for patients with documented renal impairment (defined as 
screening eGFR ≥40 to <60 mL/min/1.73 m2) is detailed in Section 5.5.1.
The dose adjustment for renal impairment will be managed by IWRS to ensure maintenance of 
the treatment blind.  The eGFR value from the screening visit (Visit 1) will be entered into IWRS 
at Visit 2, and IWRS will assign the treatment doses accordingly.
Patients with documented renal impairment (defined as screening eGFR ≥40 to
<60 mL/min/1.73 m2), who are randomized to the 4-mg active treatment arm will receive a dose 
of 2-mg QD by the IWRS. For patients randomized to the 2-mg dose or 1-mg dose, there will be 
no dose adjustment based on renal function.
No dose adjustment will be made for patients with screening eGFR ≥60 mL/min/1.73 m2.  These 
patients who are randomized to active treatment will receive their assigned dose, either
baricitinib 4-mg, 2-mg, or 1-mg, respectively.
During the study, for patients with documented renal impairment when the subsequent eGFR falls 
<30 mL/min/1.73 m2, investigational product will be withheld until their eGFR becomes 
≥40 mL/min/1.73 m2, whereupon the investigational product dosing may resume.  For patients 
with screening eGFR ≥60 mL/min/1.73 m2, when the subsequent eGFR falls to 
<40 mL/min/1.73 m2, investigational product will be withheld until their eGFR becomes 
≥50 mL/min/1.73 m2, whereupon the investigational product dosing may resume (Section 8.1.1).

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7.3.
Blinding
This is a double-blind study.  To preserve the blinding of the study, a minimum number of Lilly 
personnel will see the randomization table and treatment assignments before the study is 
complete.  All study assessments will be performed by study personnel who are blinded to the 
patient’s treatment group.  Except in clinical circumstances where unblinding is required, the 
patients, investigators, Lilly study team, and any personnel interacting directly with patients or 
investigative sites will remain blinded to baricitinib and placebo assignment until after 
completion of the double-blinded treatment periods.  It is expected that the need for unblinding a 
patient’s treatment prior to completion of the double-blinded treatment periods will be extremely 
rare.  Every effort should be made to preserve the blind unless there is a compelling reason that 
knowledge of the specific treatment would alter the medical care of the patient.  In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
patient’s treatment assignment is warranted for medical management of the event.  Patient safety 
must always be the first consideration in making such a determination.  If a patient’s treatment 
assignment is unblinded, Lilly must be notified immediately.  If the investigator decides that 
unblinding is warranted, it is the responsibility of the investigator to promptly document the 
decision and rationale and notify Lilly as soon as possible.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment.  All 
unblinding events are recorded and reported by the IWRS.  If an investigator, site personnel 
performing assessments, or patient is unblinded, the patient must be discontinued from the study.  
In cases where there are ethical reasons to have the patient remain in the study, the investigator 
must obtain specific approval from a Lilly clinical research physician for the patient to continue 
in the study.
Processes to maintain blinding during the interim analysis conducted by the DMC are described 
in Section 10.3.7.1.
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 4 through Visit 28) by counting returned tablets.

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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 7.7.5.
7.7.1. 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 up to Week 104.  After 
Week 104, the continued use of emollients is encouraged. Moisturizers with 
antipruritics or antiseptics are not permitted up to Week 104.  If daily applications are 
missed, it will not be considered a protocol violation.  Emollients will not be supplied by 
the sponsor, unless required by local regulations.
o
Patients should not apply emollients on the day of their study visit prior to the 
procedures to allow for adequate assessment of skin dryness.

Background TCS therapy (e.g., triamcinolone 0.1% cream and/or hydrocortisone 2.5% 
ointment) are to be used on active lesions in Periods 2 and 3, as described in 
Section 7.7.2.

High- or ultra-high-potency TCS are only permitted as rescue therapy as described in 
Section 7.7.5 (Rescue Therapy).

During Period 4, concomitant use of TCS may be continued, as directed by the 
investigator, as per clinical practice.  

TCIs (e.g., tacrolimus and pimecrolimus), or topical PDE-4 inhibitor (i.e., crisaborole,
where approved) are permitted in place of TCS on areas where application of TCS is 
considered inappropriate by the investigator; use should be limited to problem areas 
(e.g., face, neck, skin folds, genital areas, etc.) as described in Section 7.7.2.

Phototherapy, including therapeutic phototherapy (psoralen and ultraviolet A, 
ultraviolet B, excimer laser), is permitted as rescue therapy in Periods 2 to 4 (see 
Section 7.7.5, Rescue Therapy); however, it requires a temporary interruption of 
investigational product (see Section 8.1.1).
In addition, the following therapies are permitted during the study:

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
intranasal or inhaled steroids

leukotriene inhibitors (e.g., montelukast [Singulair], zafirlukast [Accolate], and zileuton 
[Zyflo])

topical anesthetics and topical and systemic anti-infective medications

cyclosporine ophthalmic emulsion (e.g., Restasis)

nonlive seasonal vaccinations and/or emergency vaccination, such as rabies or tetanus 
vaccinations.
For those patients on stable dosing of prescription sleep medications at entry, downward dose 
adjustments or discontinuation of treatment may occur during the study.
No more than 1 intra-articular or soft tissue (bursa, tendons, and ligaments) corticosteroid injection 
is allowed up until the 16-week primary endpoint.  After 16 weeks, such injections are permitted.
Any changes to 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.
7.7.2. Use of Topical Corticosteroids
A washout period of 14 days is required for all TCS prior to randomization at Visit 2.
At baseline (Week 0, Visit 2) and up to Week 104 (Visit 22), patients will receive triamcinolone 
0.1% cream (or equivalent-potency TCS) and hydrocortisone 2.5% ointment (or 
equivalent-potency TCS).  See “Choice of Background Topical Corticosteroid” below.  
Triamcinolone 0.1% cream (moderate-potency TCS) should be applied at least once daily to 
affected areas until lesions are under control (clear or almost clear).  Patients should then switch to 
hydrocortisone 2.5% ointment (low-potency TCS) and treat previously affected areas once-daily
for 7 days and then stop.  Hydrocortisone 2.5% ointment (low-potency TCS) may also be used to 
replace triamcinolone 0.1% cream (moderate-potency TCS) on areas of thin skin (face, neck, folds, 
and genital areas) and areas with skin atrophy.
If lesions reappear during the course of the study, the patients should resume the once-daily
applications of triamcinolone 0.1% cream (moderate-potency TCS) or hydrocortisone 2.5% 
ointment (low-potency TCS) as described above.
For patients whose lesions persist or worsen despite the use of emollients and low- and/or 
moderate-potency TCS and/or patients who require daily applications on large surfaces may be 
considered for topical rescue with high- or ultra-high-potency TCS (see Section 7.7.5 for details).
On the days of study visits, topical therapy including TCS should not be applied before the patient 
has undergone all study procedures and clinical evaluations in order to allow adequate assessment 
of skin dryness.

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After Week 104, use of TCS may be continued as directed by the investigator, as per clinical 
practice. Background TCS will no longer be provided nor reimbursed to study participants by 
the sponsor, unless required by local law. 
Choice of Background Topical Corticosteroid
Where possible, triamcinolone cream 0.1% and/or hydrocortisone 2.5% ointment will be 
supplied by the sponsor for use as background TCS up to Week 104 (Visit 22).  In the event of 
these specific TCS being unavailable, an alternate, equivalent-potency TCS may be provided by 
the sponsor (see below).  Topical corticosteroid use, when supplied by the sponsor, should be 
recorded via weight of dispensed and returned tubes as indicated in the Schedule of Activities 
(Section 2). In the event that the sponsor is unable to supply TCS, commercially available 
triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment may be supplied by the sites.  

Where providing triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment is not 
possible, an equivalent-potency TCS cream and/or ointment that is in line with local 
practices can be supplied by the sites.  Refer to Appendix 7 for guidance on potency 
equivalence.  

Where possible, TCS use when supplied by the site should also be recorded via weight of 
dispensed and returned tubes, as indicated in the Schedule of Activities (Section 2); 
however, where this is not practical, this information does not need to be recorded, and 
will not be considered a protocol violation.  

If the TCS supplied by the sponsor is not considered suitable for an individual patient, an 
equivalent-potency TCS cream and/or ointment that is in line with local practices can be
supplied by the sites.  Refer to Appendix 7 for guidance on potency equivalence.
Choice of High- and Ultra-High-Potency Topical Corticosteroids for Rescue
The use and choice of specific high- or ultra-high-potency TCS for rescue is at the discretion of 
the investigator and it will not be provided by the sponsor.  The weights of dispensed and 
returned tubes of the high- and ultra-high-potency TCS are not required.
Other Topical Treatments
Investigators may also select to use TCIs and/or crisaborole in countries where approved, in 
place of TCS.  If TCIs or crisaborole are prescribed, use should be limited to problem areas (e.g., 
face, neck, skin folds, genital areas, etc.).
Use of all topical treatments for AD must be recorded in the CRF.
7.7.3. Use of Antihistamines
Antihistamine ophthalmic preparations are permitted during the study.
During Period 2, nonsedating antihistamines are permitted, including, but not limited to, 
acrivastine, bilastine, cetirizine, desloratadin, fexofenadine, levocetirizine, loratadine, 
mizolastine, and rupatadine.

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During Period 2, sedating antihistamines, including, but not limited to, alimemazine, 
chlorphenamine, clemastine, cyproheptadine, diphenhydramine, hydroxyzine, ketotifen, and 
promethazine, are not permitted and will require a 28-day washout prior to randomization.
During Periods 3, 4, and 5, there are no restrictions for antihistamine use; both sedating and 
nonsedating antihistamines are permitted.

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7.7.4. Prohibited Medications and Procedures
Prohibited Medications and Procedures Not Requiring Urgent 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, the prohibited therapy must be discontinued.  If the patient is not able 
to discontinue use of the following then investigational product will be permanently
discontinued.

topical antihistamines or sedating, systemic antihistamines in Period 2 (see Section 7.7.3,
Use of Antihistamines, for additional information).

self-treatment with tanning booth

bleach baths (swimming in chlorinated pools is permitted)
Prohibited Medications and Procedures 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), (see 
Exclusion Criterion [29])
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.

systemic corticosteroids for the treatment of an AE (if used for AD see below). 
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.

probenecid: if a patient is inadvertently started on probenecid, investigational product
should be temporarily interrupted, and can be resumed after the patient has discontinued 
probenecid. If a patient is not able to discontinue probenecid, then investigational 
product should be permanently discontinued.

phototherapy, including therapeutic phototherapy (psoralen and ultraviolet A, 
ultraviolet B, excimer laser) as rescue therapy in Period 2 or 3.  Investigational product 
should be temporarily interrupted until completion of the phototherapy.
Prohibited Medications Requiring Permanent Discontinuation of Investigational Product

any systemic therapy, investigational or commercial (approved or off-label use), used as 
rescue for the treatment of AD (including systemic corticosteroids, see Section 7.7.5, 
Rescue Therapy).

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
systemic immunosuppressive/immunomodulatory substances, including, but not limited 
to, cyclosporine, methotrexate, mycophenolate mofetil, interferon-, azathioprine,
biologic agents, or other JAK inhibitors (e.g., tofacitinib and ruxolitinib).
Note: In the event that these prohibited medications were inadvertently used, 
agreement and documentation to continue investigational product must be sought 
from sponsor.
7.7.5. Rescue Therapy
Investigators should make every attempt to conduct efficacy and safety assessments immediately 
before administering any rescue treatment.  An unscheduled visit should be used for this purpose 
if necessary.
7.7.5.1.
Rescue during Period 2: Week 0 (Visit 2) up to Week 52 (Visit 14)
Control of AD symptoms should be attempted by avoiding exacerbating factors, intensifying
emollient applications, and using only the permitted study treatments, including background TCS 
therapy (e.g., triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment) (see 
Section 7.7.2).
Rescue with High- and Ultra-High-Potency TCS
Patients whose lesions persist or worsen despite the use of emollients and background TCS 
therapy (e.g., triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment) and/or patients 
who require prolonged applications of triamcinolone 0.1% cream (moderate-potency TCS) on 
large surfaces may be considered for rescue to high- or ultra-high-potency TCS (see Appendix 7
for TCS potency).
High- or ultra-high-potency TCS may be used once daily for up to 14 consecutive days or based 
on the maximum duration recommended in the prescribing information.
It is recommended that if a patient reaches “clear” to “almost clear” skin after topical rescue, 
then high- or ultra-high-potency TCS should be stopped, and low- and/or moderate-potency TCS 
(e.g., triamcinolone 0.1%, hydrocortisone 2.5% ointment) should be used once daily for an 
additional 7 days, then stopped.
Patients rescued with high- or ultra-high-potency TCS will continue to take investigational 
product and use of topical rescue therapy will be documented in the eCRF.
Rescue with Phototherapy
Patients may also be rescued with phototherapy at the discretion of the investigator.  Patients 
rescued with phototherapy will remain in the study and be required to temporarily interrupt use 
of investigational product until completion of the phototherapy (see Section 8.1.1 for Temporary 
Interruption of Investigational Product).

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Rescue with Systemic Therapies
Patients whose disease cannot be controlled by the measures described above may be rescued to 
systemic therapies (conventional systemics or biologics).  These patients will be required to 
discontinue investigational product and proceed to the ETV before initiating systemic treatment. 
However, patients rescued to systemic therapies prior to the primary endpoint (Week 16) should 
be encouraged to continue with study visits and assessments through Visit 8.
7.7.5.2.
Rescue during Periods 3 and 4: from Week 52 (Visit 14) to Week 200
(Visit 28)
In Period 3, all patients will continue to use concomitant background TCS (e.g., triamcinolone 
0.1% cream and hydrocortisone 2.5% ointment) as described in Section 7.7. In Period 4, use of 
concomitant may continue as directed by the investigator, as per clinical practice. All patients
may be rescued at any time with high- or ultra-high-potency TCS or phototherapy as described in 
Section 7.7.
As mentioned in Sections 5.1.3 and 5.1.4, patients who reach an IGA ≥3 after entry into the 
randomized downtitration substudy will be automatically retreated with their presubstudy dose of 
baricitinib.
Patients not eligible for the substudy and who present with an IGA ≥3 at Week 52 or anytime 
thereafter will automatically be rerandomized at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 
4-mg QD, but this will only occur once. Patients randomized to baricitinib 4-mg QD at baseline
(Week 0, Visit 2) will stay on this dose for the remainder of the trial regardless of IGA.
Patients whose disease cannot be controlled by the measures described above may be rescued to 
systemic therapies (conventional systemics or biologics).  Whenever possible during this Period, 
it is recommended to wait for at least 4 weeks after the visit at which the patient has reached IGA 
≥3 to initiate rescue with systemic therapies.
Patients rescued with high- or ultra-high-potency TCS will continue to take investigational 
product and use of topical rescue therapy will be documented in the eCRF.
Patients rescued with phototherapy will remain in the trial and will be required to temporarily 
interrupt the use of investigational product until completion of the phototherapy.
Patients who need rescue with systemic therapies (conventional systemics or biologics) during
Period 3 will be required to discontinue investigational product and to proceed to the ETV before 
initiating systemic treatment.
7.8.
Treatment after the End of the Study
Period 4 will provide patients who have completed Week 104 visit and have not met criteria for 
permanent discontinuation, the possibility to remain in the trial for up to 96 additional weeks (up 
to Week 200) and thus provide patients the opportunity to continue study treatment until the 
anticipated approval of baricitinib in this indication.
After the conclusion of the study, continued access to baricitinib will not be provided.  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 of Investigational Product
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or abnormal laboratory values that may have an unclear relationship to investigational product.  
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 JAIN.4.
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table JAIN.4, specific guidance is provided for temporarily interrupting treatment and when 
treatment may be restarted.  Retest frequency and timing of follow-up laboratory tests to monitor 
the abnormal finding are 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 JAIN.4 may be restarted at the discretion of the investigator.
Table JAIN.4.
Medical and Laboratory Criteria for Temporary Interruption of 
Investigational Product
Hold Investigational Product if the Following 
Laboratory Test Results or Clinical Events Occur
Investigational Product May Be Resumed When
WBC count <2000 cells/L
(<2.00x103/L or <2.00 GI/L)
WBC count 2500 cells/L
(≥2.50x103/L or ≥2.50 GI/L)
ANC <1000 cells/L
(<1.00x103/L or <1.00 GI/L)
ANC ≥1200 cells/L
(≥1.20x103/L or ≥1.20 GI/L)
Lymphocyte count <500 cells/L
(<0.50x103/L or <0.50 GI/L)
Lymphocyte count 750 cells/L
(≥0.75x103/L or ≥0.75 GI/L)
Platelet count <75,000/L
(<75x103/L or <75 GI/L)
Platelet count 100,000/L
(≥100x103/L or ≥100 GI/L)
eGFR <40 mL/min/1.73 m2 (from serum creatinine) for 
patients with screening eGFR ≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 (from serum creatinine) for 
patients with screening eGFR ≥40 to <60 mL/min/1.73 m2
eGFR 40 mL/min/1.73 m2
ALT or AST >5 x ULN
ALT and AST return to <2 x ULN, and IP is not 
considered to be the cause of enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 10 g/dL (≥100.0 g/L)
Symptomatic herpes zoster
All skin lesions have crusted and are resolving
Infection that, in the opinion of the investigator, merits the 
IP being interrupted
Resolution of infection

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Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; WBC = white blood cell.
Although temporary interruption of investigational product is not a requirement at times of 
increased potential risk of VTE (e.g., surgery, significant air travel, or other situations involving 
prolonged immobilization), we recommend following appropriate VTE prophylaxis guidelines to 
help manage the VTE risk under these circumstances.
For specific guidance on temporary interruption of investigational product after use of a 
prohibited medication, please refer to Section 7.7.4, Prohibited Medications and Procedures.
Lastly, investigational product should be temporarily interrupted for suicidal ideation or any 
suicide-related behaviors as assessed by the following patient responses on the C-SSRS:

A “yes” answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without 
Specific Plan) or

A “yes” answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on 
the “Suicidal Ideation” portion of the C-SSRS or

A “yes” answer to any of the suicide-related behaviors (actual attempt, interrupted 
attempt, aborted attempt, preparatory act or behavior) on the “Suicidal Behavior” portion 
of the C-SSRS.
Note:  Prior to resumption of investigational product, it is recommended that a patient be 
assessed by a psychiatrist or appropriately trained professional to assist in deciding whether the 
subject should remain on investigational product and ultimately continued participation in the 
study.  A patient does not necessarily have to have investigational product interrupted if they 
have self-injurious behavior that would be classified as nonsuicidal self-injurious behavior.
8.1.2. Permanent Discontinuation from Investigational Product
Investigational product should be permanently discontinued if the patient is rescued with 
systemic therapies to treat AD and/or 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 ULN

ALT or AST >5 x ULN for more than 2 weeks

ALT or AST >3 x ULN and total bilirubin level (TBL) >2 x ULN or international 
normalized ratio (INR) >1.5

ALT or AST >3 x ULN with the appearance of fatigue, nausea, vomiting, right 
upper-quadrant pain or tenderness, fever, and/or rash 

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 

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Note:  Patients who are discontinued from investigational product due to 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/L (1.00x103/L or 1.00 GI/L)

ANC <500 cells/L (0.50x103/L or 0.50 GI/L)

lymphocyte count <200 cells/L (0.20x103/L 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 JAIN.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.
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)

hepatitis B virus DNA is detected with a value above limit of quantitation or 2 sequential 
tests return a value of below the limit of quantitation (see Section 9.4.8).

certain prohibited medications are taken per Section 7.7.4, Prohibited Medications and 
Procedures.

development of a VTE
Note:  Patients who develop a VTE may have additional follow up and testing recommended 
(see Appendix 8).
If a patient discontinues investigational product for any reason, the patient is encouraged to 
remain in the study through Week 16 (Visit 8) and follow the regular visit schedule to provide 
the primary efficacy and safety data.  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 (CRP) agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 

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sponsor CRP to allow the inadvertently enrolled patient to continue in the study with or without 
treatment with investigational product. Safety follow-up is as outlined in Section 2 (Schedule of 
Activities), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of the protocol.
8.2.
Discontinuation from the Study
Patients will be discontinued in the following circumstances:

enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study

participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

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 systemic therapeutic 
agent (not allowed as part of rescue therapy [Section 7.7.5]) 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.
Note:  Patients rescued to systemic therapies prior to the primary endpoint 
(Week 16) will be encouraged to continue with study visits and assessments 
through Visit 8.

subject decision
o
the patient requests to be withdrawn from the study.

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.
Patients discontinuing from the study prematurely for any reason should complete adverse event 
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 Assessment
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). 
Body surface area affected by AD will be derived from data collected as part of the EASI 
assessment.
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 investigator’s global assessment of the patient’s overall severity of their AD, based 
on a static, numeric 5 point scale from 0 (clear) to 4 (severe).  The score is based on an overall 
assessment of the degree of erythema, papulation/induration, oozing/crusting, and 
lichenification. 
9.1.2.2.
SCORing Atopic Dermatitis
The SCORing Atopic Dermatitis (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 and Taieb 1993; Oranje et al 2007).
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 and in countries where the questionnaires have been translated into the 
native language of the region and linguistically validated.

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9.1.3.1.
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 (e.g., 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).
9.1.3.2.
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 to 2 days,” “3 to 4 days,” “5 to 6 days,” 
and “Every day” with corresponding scores of 0, 1, 2, 3, and 4, respectively.  Scores range from 
0 to 28, with higher total scores indicating greater disease severity (Charman et al. 2004).
9.1.3.3.
Itch Numeric Rating Scale
The Itch Numeric Rating Scale (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.”  
The 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).
9.1.3.4.
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 last night.  Patients 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 last 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.
9.1.3.5.
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.” The 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 past 24 hours.
9.1.3.6.
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.”

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9.1.3.7.
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 lot,” and “very much,” with corresponding scores of 
1, 2, and 3, respectively, and unanswered (“not relevant”) responses scored as 0. Scores range 
from 0 to 30, with higher scores indicating greater impairment of QoL. A DLQI total score of 0 
to 1 is considered as having no effect on a patient’s health-related QoL (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).
9.1.3.8.
European Quality of Life–5 Dimensions–5 Levels
The European Quality of Life–5 Dimensions–5 Levels (EQ-5D-5L) is a standardized measure of 
health status 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 ticking (or placing a cross) in the box associated with 
the most appropriate statement in each of the 5 dimensions.  It should be noted that the numerals 
1 to 5 have no arithmetic properties and should not be used as an ordinal score.  The VAS 
records the respondent’s self-rated health on a vertical VAS where the endpoints are labeled 
“best imaginable health state” and “worst imaginable health state.”  This information can be used 
as a quantitative measure of health outcome.  The EQ-5D-5L health states, defined by the 
EQ-5D-5L descriptive system, may be converted into a single summary index by applying a 
formula that essentially attaches values (also called weights) to each of the levels in each 
dimension (Herdman et al. 2011; EuroQol Group 2015 [WWW]).
9.1.3.9.
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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9.1.3.10. Medical Outcomes Study 36-Item Short Form Health Survey Version 2 
Acute (SF-36)
The SF-36v2 Acute measure is a subjective, generic, health-related QoL instrument that is 
patient reported and consists of 36 questions covering 8 health domains: physical functioning, 
bodily pain, role limitations due to physical problems, role limitations due to emotional 
problems, general health perceptions, mental health, social function, and vitality (Ware and 
Sherbourne 1992). Each domain is scored by summing the individual items and transforming the 
scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. In 
addition, 2 summary scores, the PCS (physical component score) and the MCS (mental 
component score), will be evaluated based on the 8 SF-36v2 Acute domains.
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.
The investigator will record all relevant AE and SAE information in the eCRF.  After the ICF is 
signed, study site personnel will record in the 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 

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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

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 disposition CRF has been completed).  

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However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
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.  
US 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 identification,
recording, and expedited reporting of SUSARs that are consistent with global regulations and the 
associated detailed guidances.
9.2.2. Adverse Events of Special Interest
Adverse events of special interest will include the following:

infections (including TB, herpes zoster, or opportunistic infections)

malignancies (except for successfully treated basal or squamous cell skin carcinoma)

hepatic events (see Section 9.4.10)

major adverse cardiovascular events (MACE) (see Section 9.4.9)

thrombotic events (such as deep vein thrombosis and pulmonary embolism).
Sites will provide details on these AEs as instructed on the eCRF and may be asked for 
additional description by Lilly.
9.2.3. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
Refer to the IB.
9.4.
Safety
Any clinically significant findings from ECG testing, physical examination, vital signs 
measurements, or laboratory measurements that result in a diagnosis and that occur after the 
patient receives the first dose of study treatment should be reported to Lilly or its designee as an 
AE via eCRF.

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9.4.1. Electrocardiograms
A single 12-lead standard ECG will be obtained locally at Visit 1 and read by a qualified 
physician (the investigator or qualified designee) at the site to determine whether the patient 
meets entry criteria.
Electrocardiograms may be obtained at additional times, when deemed clinically necessary.
9.4.2. Vital Signs
For each patient, vital signs should be measured according to the Schedule of Activities 
(Section 2).
9.4.3. Physical Examination
For each patient, a complete physical examination (excluding pelvic and rectal examinations) 
will be performed at Visit 1 (Screening).  A symptom-directed physical examination will be 
performed at other visits as specified in the Schedule of Activities (Section 2).  A complete 
physical examination may be repeated at the investigator’s discretion at any time a patient 
presents with physical complaints.
9.4.4. Laboratory Tests
For each patient, laboratory tests detailed in Appendix 2 should be conducted according to the 
Schedule of Activities (Section 2).  With the exception of laboratory test results that may unblind 
the study, Lilly or its designee will provide the investigator with the results of laboratory tests 
analyzed by a central vendor, if a central vendor is used for the clinical trial.
9.4.5. Columbia Suicide Severity Rating Scale
The C-SSRS captures the occurrence, severity, and frequency of suicidal ideation and/or 
behavior during the assessment period.  The scale includes suggested questions to solicit the type 
of information needed to determine if suicidal ideation and/or behavior occurred.  The C-SSRS is 
administered by an appropriately trained health care professional with at least 1 year of patient 
care/clinical experience.  The tool was developed by the National Institute of Mental Health trial 
group for the purpose of being a counterpart to the Columbia Classification Algorithm of Suicide 
Assessment categorization of suicidal events.  For this study, the scale has been adapted (with 
permission from the scale authors) to include only the portion of the scale that captures the 
occurrence of the 11 preferred ideation and behavior categories.
The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.

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9.4.6. 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.
9.4.7. Chest x-ray and Tuberculosis Testing
A posterior–anterior view chest x-ray will be obtained locally at screening (Visit 1), unless 
results from a chest x-ray obtained within 6 months prior to the study are available.  The chest 
x-ray will be reviewed by the investigator or his or her designee to exclude patients with active 
TB infection.  In addition, patients will be tested at screening (Visit 1) for evidence of active or 
latent TB as described in the exclusion criteria (Section 6.2).
Investigators should follow local guidelines for monitoring patients for TB if a patient is at high 
risk for acquiring TB or reactivation of latent TB.
9.4.8. Hepatitis B Virus DNA Monitoring
Patients who are HBcAb positive and HBV DNA negative (undetectable) at Visit 1 will require 
periodic measurement of HBV DNA as per study schedule (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,” 
HBV DNA monitoring will be performed per study schedule (Section 2).

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.
9.4.9. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, only members of the DMC (an advisory group for this study formed to protect 
the integrity of data; refer to Interim Analyses section [Section 10.3.7]) can conduct additional 
analyses of the safety data.
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 

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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 in a blinded manner by Lilly during the clinical 
trial.  These reports will be reviewed to ensure completeness and accuracy but will not be 
unblinded to Lilly during the clinical trial.  If a death or a clinical AE is deemed serious, 
unexpected, and possibly related to investigational product, only Lilly Global Patient Safety will 
be unblinded for regulatory reporting and safety monitoring purposes.  These measures will 
preserve the integrity of the data collected during this trial and minimize any potential for bias 
while providing for appropriate safety monitoring.
Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular and venous thrombotic events.  Adverse event reports and vital signs will be 
collected at each study visit.  The cardiovascular monitoring plan includes the following:

regular monitoring of lipid levels

potential MACE (cardiovascular death, 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), venous thrombotic 
events, and noncardiovascular deaths will be identified by the investigative site or 
through medical review and will be sent to a blinded Clinical Event Committee for 
adjudication at regular intervals.
9.4.10. Hepatic Safety Monitoring
If a study patient experiences elevated ALT ≥3 x ULN, ALP ≥2 x ULN, or elevated TBL ≥2 x 
ULN, liver testing (Appendix 4) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor.  Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels.
Discontinuation criteria of investigational products, either temporary interruption or permanent 
discontinuation, due to abnormal ALT, AST, TBL, or ALP, are detailed in Section 8.1.
9.4.10.1. Hepatic Safety Data Collection
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

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
patient discontinued from treatment due to 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 interruption or permanent discontinuation of investigational 
product, or additional safety collection via the hepatic eCRF.
9.5.
Pharmacokinetics
Not applicable.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenetics
9.7.1. Blood Samples for Pharmacogenetic Research
A blood sample will be collected for pharmacogenetic analysis as specified in the Schedule of 
Activities (Section 2) where local regulations allow.
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to investigational 
product and to investigate genetic variants thought to play a role in AD.  Assessment of variable 
response may include evaluation of AEs or differences in efficacy.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained at a facility selected by Lilly for a maximum of 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and/or ethical review boards 
(ERBs)/investigational review boards (IRBs) impose shorter time limits. 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.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome-wide association studies, and candidate gene studies.  Regardless of 
technology utilized, genotyping data generated will be used only for the specific research scope 
described in this section.
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics, mechanism of action, variability of patient response (including 
safety), and clinical outcome.  Sample collection is incorporated into clinical studies to enable 

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examination of these questions through measurement of biomolecules including DNA, RNA, 
proteins, lipids, and other cellular elements.
Blood samples for biomarker research will be collected at the times specified in the Schedule of 
Activities (Section 2) where local regulations allow.
Samples will be used for research on the drug target, disease process, variable response to 
baricitinib, pathways associated with AD, mechanism of action of baricitinib, and/or research 
method or in validating diagnostic tools or assay(s) related to AD.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.
Samples will be retained at a facility selected by Lilly for a maximum of 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and ERBs impose shorter 
time limits.  This retention period enables use of new technologies, response to regulatory 
questions, and investigation of variable response that may not be observed until later in the 
development of baricitinib.
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
Study JAIN will aim to enroll 500 patients ≥18 years of age.  Ignoring stratification, the 
proposed sample size will ensure a >90% power based on the Chi-square test to detect an 
absolute difference of approximately 25% between the 4-mg baricitinib and the placebo 
treatment groups, and the 2-mg baricitinib and the placebo treatment groups, each using a 
2-sided alpha of 0.025 and assuming approximately 20% placebo response rate for the primary 
endpoint. These assumptions are based on what was observed in the Phase 3 study (JAIY).  
Sample size and power estimates were obtained from nQuery® Advisor 7.0.
10.2. Populations for Analyses
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the 
intent-to-treat population, defined as all randomized patients, even if the patient does not receive 
the correct treatment, or otherwise did not follow the protocol.  
Unless otherwise specified, safety analyses will be conducted on all randomized patients who 
receive at least 1 dose of investigational product they were randomized to in Study JAIN and 
who did not discontinue from the study for the reason “Lost to Follow-up” at the first 
postbaseline visit.  
Patients will be analyzed for efficacy, health outcomes, and safety according to the treatment to 
which they were assigned.  Further details will be described in the SAP, including but not limited 
to, additional populations for the randomized down-titration substudy.  Significant protocol 
violations will be described in the SAP.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee.  A detailed 
SAP describing the statistical methodologies will be developed by Lilly or its designee.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated.  Treatment comparisons of discrete efficacy variables between baricitinib and placebo 
will be made using a logistic regression analysis with baseline disease severity (vIGA AD), 
baseline score and treatment group in the model.  Region may be added as an additional factor if 
the planned country allocation justifies, and stratification has not resulted in empty strata. This 
will be finalized in the SAP. If appropriate, treatment-by-region interaction may be added to the 

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model of the primary and key secondary variables as a sensitivity analysis. If this interaction is 
significant at a 2-sided 0.1 level, further inspection will be used to assess whether the interaction 
is quantitative (i.e., the treatment effect is consistent in direction but not size of the effect) or 
qualitative (the treatment is beneficial for some but not all regions).  The percentages, difference 
in percentages, and 95% confidence interval (CI) of the difference in percentages will be 
reported.  The p-value from the Fisher exact test will also be produced.  Additional relative 
measures, for example, odds ratio, may be reported as appropriate.
When evaluating continuous measures over time, a restricted maximum likelihood-based mixed 
model for repeated measures (MMRM) will be used.  The model will include treatment, baseline 
severity (vIGA AD), visit, and treatment-by-visit interaction as fixed categorical effects and 
baseline score and baseline score-by-visit interaction as fixed continuous effects.  Region may be 
added as an additional factor if the planned country allocation justifies. An unstructured 
(co)variance structure will be used to model the between- and within-patient errors.  If this 
analysis fails to converge, other structures will be tested.  The Kenward–Roger method will be 
used to estimate the degrees of freedom.  Type III sums of squares for the least squares means 
(LSMs) will be used for the statistical comparison; 95% CI will also be reported.  Contrasts will 
be set up within the model to test treatment groups at specific time points of interest.  Further 
details on the use of MMRM will be described in the SAP.
Treatment comparisons of continuous efficacy and health outcome variables may also be made 
using analysis of covariance (ANCOVA) with disease severity, treatment group, and baseline 
value in the model.  Region may be added as an additional factor if the planned country 
allocation justifies. Type III tests for LSMs will be used for statistical comparison between 
treatment groups.  The LSM difference, standard error, p-value, and 95% CI may also be 
reported.  The methods used to handle missing data will be specified in the SAP.
Time-to-event analysis may be done and would be analyzed using a Cox proportional hazards 
model with disease severity and treatment group in the model.  Region may be added as an 
additional factor if the planned country allocation justifies. Hazard ratio with CIs may be 
reported.  Kaplan–Meier curves may also be produced.  Diagnostic tests for checking the validity 
of the proportional hazards assumption may be performed and these would be described in detail 
in the SAP.  If the assumption of proportional hazards is not justified, nonproportionality may be 
modeled by stratification, as the most likely variable that interacts with time is categorical, that 
is, disease severity.
Fisher exact test will be used for the AEs, discontinuation, and other categorical safety data for 
between-treatment group comparisons.  Continuous vital signs, body weight, and other 
continuous safety variables including laboratory variables will be analyzed by an ANCOVA with 
treatment and baseline value in the model.  Shift tables for categorical safety analyses (e.g., 
“high” or “low” laboratory results) will also be produced.

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10.3.1.1. Missing Data Imputation

Nonresponder imputation (NRI):  All patients who discontinue the study or the study 
treatment at any time for any reason will be defined as nonresponders for the NRI 
analysis for categorical variables such as IGA 0/1 or EASI50/75/90 from the time of 
discontinuation and onward.  Patients who receive rescue therapy (high or ultra-high 
potency TCS, phototherapy, or systemic therapies for treatment of AD, see
Section 7.7.5) will be analyzed as nonresponders from the point of rescue and 
onward.  An additional analysis will be performed that includes all available data 
regardless of whether rescue medication was given or not.

Continuous variables such as EASI and SCORAD scores will be assumed to be 
missing from the point of rescue or discontinuation and then an MMRM analysis will 
be performed.  An additional analysis will be performed that includes all available 
data regardless of whether rescue medication was given or not.

Last observed carried forward:  An additional analysis will be performed that uses the 
last observed value prior to discontinuation or rescue therapy.  This will then be 
analyzed using a logistic model for categorical variables or ANCOVA for continuous 
variables as described above.
There will be further discussion on the relevant estimands including appropriate methods for 
analysis and imputation of missing data in the SAP.  This will include specifications of 
additional sensitivity analyses for the primary and key secondary endpoints such as tipping point 
as well as a reference-based multiple imputation method.
10.3.1.2. Adjustment for Multiple Comparisons
Multiplicity controlled analyses will be conducted on the primary and major secondary endpoints 
in order to control the overall family-wise type I error rate at a 2-sided level of 0.05.  The 
graphical multiple testing procedure described in Bretz et al. (2011) will be used.  The graphical 
approach is a closed testing procedure, hence it strongly controls the family-wise error rate 
across all endpoints (Alosh et al. 2014).  Details of the specific graphical testing scheme 
(including testing order, interrelationships, type I error allocation, and the associated 
propagation) will be prespecified in the SAP.
The following is a list of primary and key secondary endpoints to be tested:
Primary:

proportion of baricitinib 4-mg + TCS patients achieving EASI75 at Week 16

proportion of baricitinib 2-mg + TCS patients achieving EASI75 at Week 16
Key Secondaries:

proportion of baricitinib 1-mg + TCS patients achieving EASI75 at Week 16
Evaluated for 4-mg + TCS, 2-mg + TCS, and 1-mg + TCS:

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
proportion of patients achieving IGA of 0 or 1 and ≥2-point improvement from 
baseline at 16 weeks

proportion of patients achieving EASI90 at 16 weeks

percent change from baseline in EASI score at 16 weeks

proportion of patients achieving SCORAD75 at 16 weeks

proportion of patients achieving a 4-point improvement in Itch NRS at 16 weeks

proportion of patients achieving a 4-point improvement in Itch NRS at 4 weeks

proportion of patients achieving a 4-point improvement in Itch NRS at 2 weeks

proportion of patients achieving a 4-point improvement in Itch NRS at 1 week

mean change from baseline in the total score of Item 2 of the ADSS at 16 weeks

mean change from baseline in the total score of Item 2 of the ADSS at 1 week

mean change from baseline in Skin Pain NRS at 16 weeks

proportion of patients achieving IGA of 0 or 1 with a ≥2-point improvement at 
Week 24

proportion of patients achieving EASI75 at 24 weeks.
10.3.1.3. Adjustment for Unblinding of Primary Analyses 24-Week Data
When all patients have completed their Week 24 assessments, the primary analysis for the 
purpose of regulatory submission will be made. The evaluation of the primary and key 
secondary endpoints will be adjusted for multiplicity. 
Although the regulatory submission team will be unblinded to the 24-week data and to patient 
treatment assignments, they will not have access to efficacy data after 24 weeks until all patients 
have completed Week 52.  In order to maintain the blind for efficacy data beyond Week 24, 
post-lock activities will incorporate appropriate security measures, including restricted provision 
of data. The study team preparing for the submission is authorized to evaluate unblinded 
efficacy and safety analyses.  Study sites will not receive any patient level efficacy and safety 
information. Unblinding details will be specified in a separate unblinding plan document to 
ensure proper firewalls between the study team and study sites.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
All patients who discontinue from the study or the study treatment will be identified, and along 
with their reason for discontinuation.  Reasons for discontinuation from the study will be 
summarized by treatment group.  This will be done for Period 2 and Period 3 of the study.  
Additional summaries that may be produced for other populations will be documented in the 
SAP.  Reasons for discontinuation from the study will be summarized by treatment group and 
compared between groups with Fisher exact test.

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10.3.2.2. Patient Characteristics
Demographic and baseline characteristics will be summarized descriptively by treatment group
for Period 2 and Period 3 of Study JAIN.  Additional summaries that may be produced for other 
populations will be documented in the SAP.  Descriptive statistics including number of patients, 
mean, standard deviation, median, minimum, and maximum will be provided for continuous 
measures, and frequency counts and percentages will be tabulated for categorical measures.  No 
formal statistical comparisons will be made among treatment groups unless otherwise stated.
10.3.2.3. Concomitant Therapy
Concomitant medications will be descriptively summarized by treatment group in terms of 
frequencies and percentages. The medications will be coded accordingly.
10.3.2.4. Treatment Compliance
Treatment compliance with the randomly assigned 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, i.e., 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, i.e., compliance ≥120%.
10.3.3. Efficacy Analyses
10.3.3.1. Primary Analyses
The primary efficacy measure is categorical outcome of EASI75 at Week 16.  EASI75 is defined 
as having an improvement of at least 75% from baseline.  Primary analysis will be conducted 
using a logistic regression as described above with treatment and the stratification variables 
(disease severity; region as appropriate) in the model, to test the treatment difference in 
proportion.  Nonresponder imputation for missing data as described above will be used.
Additional analysis of the primary efficacy outcome will include analyzing the outcome as 
observed, i.e., whether or not rescue medication was used.
10.3.3.2. Secondary Analyses
The following secondary categorical outcomes will be analyzed in a similar manner as the 
primary, i.e., using the same logistic regression model.  Nonresponder imputation will be used 
for these analyses unless otherwise noted.

IGA score of 0 or 1 (clear or almost clear skin) and ≥2-point improvement 
from baseline at Week 16. Besides NRI, this outcome will also be analyzed 
using observed cases, that is, whether rescue medication was given.

EASI75 at Week 52, Week 24, and Week 4.  EASI75 is defined as having an 
improvement of at least 75% from baseline. Besides NRI, this outcome will also be 
analyzed using observed cases, i.e., whether rescue medication was given or not.

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
EASI90 at Week 16.  EASI90 is defined as having an improvement of at least 90% 
from baseline

EASI50 at Week 16.  EASI50 is defined as having an improvement of at least 50% 
from baseline

SCORAD75 at Week 16.  SCORAD75 is defined as having an improvement of at 
least 75% from baseline.

SCORAD90 at Week 16.  SCORAD90 is defined as having an improvement of at 
least 90% from baseline.

4-point improvement in Itch NRS at 24 weeks, 16 weeks, 4 weeks, 2 weeks, and 
1 week

IGA score of 0 or 1 (clear or almost clear skin) and ≥2-point improvement from 
baseline at Week 52, Week 24, and Week 4

IGA of 0 at 16 weeks
The following continuous measures will be analyzed with the MMRM model described above 
unless otherwise noted.  Contrasts within the MMRM model will be used to assess treatment 
differences for time points of interest as specified above in the list of objectives.

Mean change from baseline in the following outcome measures:

ADSS Items 1, 2 and 3

EASI score

SCORAD score

Body Surface Area

Itch NRS

Skin Pain NRS

POEM total score

PGI-S-AD

HADS

DLQI total score

WPAI-AD

EQ-5D-5L
The EASI total score and SCORAD total score will also be analyzed as observed, i.e., not 
assuming missing values after rescue medication is given.
The following categorical data will be analyzed using Fisher exact test described above unless 
otherwise noted.

Patients requiring rescue with high- or ultra-high-potency TCS

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
Patients requiring rescue with systemic treatments
The following measures will be analyzed by an ANCOVA with treatment and baseline value in 
the model.

Mean number of days without use of background TCS over 16 weeks

Mean gram quantity of background TCS used over 16 weeks (tube weights)
10.3.4. Safety Analyses
All safety data will be descriptively summarized by treatment groups and analyzed using the 
safety population, unless otherwise stated.
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 MedDRA 
(Medical Dictionary for Regulatory Activities) for each system organ class (or a body system) 
and each preferred term by treatment group. Serious adverse events and AEs that lead to 
discontinuation of investigational product will also be summarized by treatment group. Fisher 
exact test will be used to perform comparisons between each baricitinib dose and the placebo 
group. Further details will be provided in the SAP.
All clinical laboratory results will be descriptively summarized by treatment group. 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 by treatment group and analyzed using
ANCOVA with treatment and baseline value in the model. Categorical variables, including the
incidence of abnormal values and incidence of adverse events of 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 descriptively summarized by treatment group and time point.  
Change from baseline to postbaseline in vital signs, and body weight will be analyzed using 
ANCOVA with treatment and baseline value in the model.
The incidence and average duration of investigational product interruptions will be summarized 
and compared descriptively among treatment groups. Various techniques may be used to 
estimate the effects of investigational product interruptions on safety measures. Further analyses 
may be performed and will be planned in the SAP.
Data collected after initiation of rescue therapy will be summarized as appropriate.
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
Not applicable.

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10.3.6. Other Analyses
10.3.6.1. Health Economics
The health outcome measures will be analyzed using methods described for continuous or 
categorical data as described for efficacy measures in Section 9.1.3.  More detailed analytical 
methods will be described in the SAP.
10.3.6.2. Subgroup Analyses
To assess whether the treatment effect is similar across subgroups for the primary efficacy 
outcome, a logistic model will be used and will include treatment, stratification variables 
(disease severity; region as appropriate), the subgroup variable (e.g., sex), and the 
subgroup-by-treatment interaction.  If the interaction is statistically significant at alpha = 0.10, 
the nature of the interaction will be explored, that is, within each subgroup the treatment effect 
will be estimated.  Similarly, for the continuous variables of EASI, the MMRM model will 
include additional variables for subgroup and the subgroup by treatment interaction.
Treatment effects for subgroups defined by IGA, age, race, sex, and region (as appropriate) will 
be assessed and reported regardless of whether the interaction test is significant or not.
10.3.7. Interim Analyses
10.3.7.1. Data Monitoring Committee
A DMC will oversee the conduct of this trial.  The DMC will consist of members external to 
Lilly.  This DMC will follow the rules defined in the DMC charter, focusing on potential and 
identified risks for this molecule and for this class of compounds.  Data Monitoring Committee 
membership will include, at a minimum, specialists with expertise in dermatology, statistics, and 
other appropriate specialties.
The DMC will be authorized to review unblinded results of analyses by treatment group prior to 
database lock, including study discontinuation data, AEs including SAEs, clinical laboratory 
data, vital sign data, etc.  Only the DMC is authorized to evaluate unblinded interim efficacy and 
safety analyses.  Study sites will receive information about interim results ONLY if they need to 
know for the safety of their patients. The DMC may recommend continuation of the study, as 
designed; temporary suspension of enrollment; or the discontinuation of a particular dose 
regimen or the entire study.  Although the DMC may request to review efficacy data to 
investigate the benefit/risk relationship in the context of safety observations for ongoing patients 
in the study, no information regarding efficacy will be communicated.  Moreover, the study will 
not be stopped for positive efficacy results nor will it be stopped for futility.  Hence, no alpha is 
spent.  Details of the DMC, including its operating characteristics, will be documented in a DMC 
charter and DMC analysis plan.
10.3.7.2. Adjudication Committee
A blinded 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 

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revascularization such as coronary artery bypass graft or percutaneous coronary intervention), 
venous thrombotic events, and noncardiovascular deaths.  Details of membership, operations, 
recommendations from the Committee, and the communication plan will be documented in the 
Charter.
10.3.7.3. Unblinded Study Team for the Primary Analyses for Regulatory 
Submission
A limited number of pre-identified individuals will have access to the 24-week unblinded data
when all the patients complete Week 24 assessments. These individuals will not have access to 
efficacy data after 24 weeks until all patients have completed Week 52. In order to maintain the 
blind for efficacy data beyond Week 24, post-lock activities will incorporate appropriate security 
measures, including restricted provision of data. Only the blinded study team will communicate 
with sites on regular trial conduct issues, and study sites will not receive any patient level
efficacy and safety information from the primary analyses for submission.
10.3.7.4. Other Interim Analyses
Besides DMC members and Unblinded Study Team for the Primary Analyses for Regulatory 
Submission, a limited number of pre-identified individuals may gain access to the limited 
unblinded data, as specified in the unblinding plan, prior to the primary analysis or final database 
lock for preparation of regulatory documents. Interim locks will be conducted at various 
timepoints to support regulatory submissions and scientific disclosures.  The timing of the data 
lock(s) for the analysis of the efficacy data from the sub-study will be determined by the 
retreatment rates. Information that may unblind the study during the analyses will not be 
reported to study sites or blinded study team until the study has been unblinded.
Unblinding details will be specified in a separate unblinding plan document to ensure proper 
firewalls between the unblinded study team and study sites.

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11.
References
Alosh M, Bretz F, Huque M. Advanced multiplicity adjustment methods in clinical trials. Stat 
Med. 2014;33(4):693-713.
Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically 
important difference and responsiveness of the Dermatology Life Quality Index (DLQI): 
further data. Dermatology. 2015;230(1):27-33.
Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483-1494.
Bieber T. Atopic dermatitis. Ann Derm. 2010;22(2):125-137.
Bieber T, Straeter B. Off-label prescriptions for atopic dermatitis in Europe. Allergy. 
2015;70(1):6-11.
Bożek A, Reich, A. Assessment of Intra- and Inter-Rater Reliability of Three Methods for 
Measuring Atopic Dermatitis Severity: EASI, Objective SCORAD, and IGA. Dermatology. 
2017;233(1):16-22.
Bretz F, Posch M, Glimm E, Klinglmueller F, Maurer W, Rohmeyer K. Graphical approaches for 
multiple comparison procedures using weighted Bonferroni, Simes, or parametric tests. Biom 
J. 2011;53(6):894-913.
Charman CR, Venn AJ, Williams HC. The Patient-Oriented Eczema Measure. Arch Dermatol.
2004;140:1513-1519.
Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors 
for inflammatory diseases. J Med Chem. 2014;57(12):5023-5038.
Divekar R, Kita H. Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic 
stromal lymphopoietin) and allergic inflammation. Curr Opin Allergy Clin Immunol. 
2015;15(1):98-103.
Dougados M, van der Heijde D, Chen YC, Greenwald M, Drescher E, Liu J, Beattie S, Witt S, de 
la Torre I, Gaich C, Rooney T, Schlichting D, de Bono S, Emery P. Baricitinib in patients with 
inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-
BUILD study. Ann Rheum Dis. 2017;76(1):88-95.
Dupixent [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 2017.
Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, 
Bergman JN, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Krol A, Margolis DJ, Paller 
AS, Schwarzenberger K, Silverman RA, Williams HC, Elmets CA, Block J, Harrod CG, Smith 
Begolka W, Sidbury R. Guidelines of care for the management of atopic dermatitis: Section 1. 
Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-351.
EuroQol Group. EQ-5D-5L User Guide. Version 2.1. April 2015. Available at: 
https://euroqol.org/wp-content/uploads/2016/09/EQ-5D-5L_UserGuide_2015.pdf. Accessed 
October, 2017.
Fleischmann R, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, Zerbini 
CA, Gurbuz S, Dickson C, de Bono S, Schlichting D, Beattie S, Kuo WL, Rooney T, Macias 
W, Takeuchi T. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis 

I4V-MC-JAIN(e) Clinical Protocol
Page 84
LY3009104
and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol. 
2017;69(3):506-517.
Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, 
Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis 
G, Newton RC, Metcalf B, Friedman SM, Vaddi K. Selective inhibition of JAK1 and JAK2 is 
efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J 
Immunol. 2010;184(9):5298-5307.
Futamura M, Leshem YA, Thomas KS, Nankervis H, Williams HC, Simpson EL. A systematic 
review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: Many 
options, no standards. J Am Acad Dermatol. 2016;74(2):288-294.
Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, 
Cardillo TE, Rooney TP, Macias WL, de Bono S, Schlichting DE, Smolen JS. Baricitinib in 
patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243-1252.
Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and 
severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. 
Exp Dermatol. 2001;10(1):11–18.
Herdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, Bonsel G, Badia X.
Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L).
Qual Life Res. 2011;20(10):1727-1736.
Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY. Translating the science of quality 
of life into practice: What do dermatology life quality index scores mean? J Invest Dermatol. 
2005;125(4):659-664.
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.
Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric 
population. Pediatrics. 2008;122(4):812-824.
Langenbruch A, Radtke M, Franzke N, Ring J, Foelster-Holst R, Augustin M. Quality of health 
care of atopic eczema in Germany: results of the national health care study AtopicHealth. J 
Eur Acad Dermatol Venereol. 2014;28(6):719-726.
Langley RG, Feldman SR, Nyirady J, van de Kerkhof P, Papavassilis C. The 5-point 
Investigator’s Global Assessment (IGA) Scale: A modified tool for evaluating plaque psoriasis 
severity in clinical trials. J Dermatolog Treat. 2015;26(1):23-31.
Li M, Messaddeq N, Teletin M, Pasquali JL, Metzger D, Chambon P. Retinoid X receptor 
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.
Moniaga CS, Jeong SK, Egawa G, Nakajima S, Hara-Chikuma M, Jeon JE, Lee SH, Hibino T, 
Miyachi Y, Kabashima K. Protease activity enhances production of thymic stromal 

I4V-MC-JAIN(e) Clinical Protocol
Page 85
LY3009104
lymphopoietin and basophil accumulation in flaky tail mice. Am J Pathol. 
2013;182(3):841-851.
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. 
2015;138(6):1548-1555.
Oranje AP, Glazenburg EJ, Wolkerstorfer A, de Waard-van der Spek FB. Practical issues on 
interpretation of scoring atopic dermatitis: the SCORAD index, objective SCORAD and the 
three-item severity score. Br J Dermatol. 2007;157(4):645-8. 
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, 
Compton JG, DiGiovanna JJ, Fleckman P, Lewis-Jones S, Arseculeratne G, Sergeant A, 
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;38:441-446.
Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, Macias W, Zhang X, Janes 
JM. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, 
in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016;174(6):1266-1276.
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. Pharmacoeconomics. 1993;4(5):353-365.
Simpson EL. Comorbidity in atopic dermatitis. Curr Dermatol Rep. 2012;1(1):29-38.
Snaith RP. The Hospital Anxiety and Depression Scale. Health and Quality of Life Outcomes. 
2003;1:29. Available at: http://www.hqlo.com/content/1/1/29. Accessed February, 2017.
Stalder J, Taieb 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.
Tadicherla S, Ross K, Shenefelt PD, Fenske NA. Topical corticosteroids in dermatology. J 
Drugs Dermatol. 2009;8(12):1093-1105.
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. Baricitinib versus placebo or adalimumab in rheumatoid 
arthritis. N Engl J Med. 2017;376:652-662.
Tuttle KR, Brosius FC, Adler SG, Kretzler M, Mehta RL, Tumlin JA, Liu J, Silk ME, Cardillo 
TE, Duffin KL, Haas JV, Macias WL, Janes JM. Baricitinib in diabetic kidney disease: Results 
from a Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Paper
presented at: Annual Meeting of the American Diabetes Association; 5–9 June 2015; Boston, 
MA.
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.

I4V-MC-JAIN(e) Clinical Protocol
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Ware JE Jr, Sherbourne CD. The MOS 36item short-form health survey (SF_36), I: Conceptual 
framework and item selection. Med Care. 1992;30(6):473-483.
White D, Leach C, Sims R, Atkinson M, Cottrell D. Validation of the Hospital Anxiety and 
Depression Scale for use with adolescents. Br J Psychiatry. 1999;175(5):452-454.
[WHO] World Health Organization. Model Prescribing Information: Drugs used in skin diseases. 
1997; Geneva.
Wilson SR, Thé L, Batia LM, Beattie K, Katibah GE, McClain SP, Pellegrino M, Estandian DM, 
Bautista DM. The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to 
induce itch. Cell. 2013;155(2):285-295.
Wollenberg A, Oranje A, Deleuran M, Simon D, Szalai Z, Kunz B, Svensson A, Barbarot S, von 
Kobyletzki L, Taieb A, de Bruin-Weller M, Werfel T, Trzeciak M, Vestergard C, Ring J, 
Darsow U; European Task Force on Atopic Dermatitis/EADV Eczema Task Force.
ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic 
dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol. 2016;30(5):729-747.
Yano C, Saeki H, Ishiji T, Ishiuji Y, Sato J, Tofuku Y, Nakagawa H. Impact of disease severity 
on sleep quality in Japanese patients with atopic dermatitis. J Dermatol Sci. 
2013;72(2):195-197.
Zhong J, Sharma J, Raju R, Palapetta SM, Prasad TS, Huang TC, Yoda A, Tyner JW, van 
Bodegom D, Weinstock DM, Ziegler SF, Pandey A. TSLP signaling pathway map: a platform 
for analysis of TSLP-mediated signaling. Database. 2014; Article ID bau007, 
doi:10.1093/database/bau007.
Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H. The biology of thymic stromal 
lymphopoietin (TSLP). Adv Pharmacol. 2013;66:129-155.
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 
1983;67:361-370.

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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
ANC
absolute neutrophil count
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
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
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CRS
clinical research physician
C-SSRS
Columbia Suicide Severity Rating Scale
CSR
clinical study report
CyA
cyclosporine A
DLQI
Dermatology Life Quality Index
DMC
data monitoring committee
EASI
Eczema Area and Severity Index

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ECG
electrocardiogram
eCOA
electronic clinical outcome assessment
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.
EQ-5D-5L
the European Quality of Life–5 Dimensions–5 Levels
ERB
ethical review board
ETV
early termination visit
FDA
the Food and Drug Administration
FSH
follicle-stimulating hormone
GCP
good clinical practice
HADS
Hospital Anxiety Depression Scale
HBcAb
hepatitis B core antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency 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

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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
MACE
major adverse cardiovascular events
MI
myocardial infarction
MMRM
mixed-effects model of repeated measures
NRI
nonresponder imputation
NRS
Numeric Rating Scale
PDE-4 inhibitor
phosphodiesterase type 4 inhibitor
PK
pharmacokinetic
POEM
Patient-Oriented Eczema Measure
PPD
purified protein derivative
PRO/ePRO
patient-reported outcomes/electronic patient-reported outcomes
QD
once daily
QoL
quality of life
RA
rheumatoid arthritis
SAE
serious adverse event
SAP
statistical analysis plan
SCORAD
SCORing Atopic Dermatitis
STAT
signal transducer and activator of transcription
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBL
total bilirubin level
TCNI
topical calcineurin inhibitor

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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.
TSH
thyroid-stimulating hormone
TSLP
thymic stromal lymphopoietin
ULN
upper limit of normal
US
United States
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
Hematologya,b
Clinical Chemistrya,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 (ALP)
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)e
Creatine phosphokinase (CPK)
Urinalysisa,b,d
Color
Other Testsa
Specific gravity
Hepatitis B Surface antigen (HBsAg)f
pH
Anti-Hepatitis B Core antibody (HBcAb)f
Protein
HBV DNAk
Glucose
Anti-Hepatitis B Surface antibody (HBsAb)f
Ketones
Human immunodeficiency virus (HIV)f
Bilirubin
Hepatitis C antibodyf,g
Urobilinogen
Thyroid-stimulating hormone (TSH)
Blood
Exploratory storage samples (serum, plasma and mRNA)
Leukocyte esterase
Pregnancy Testh
Nitrite
Follicle-stimulating hormonef,i
Serum immunoglobulin (IgE)
Lipidsa,c
QuantiFERON®-TB Gold or T-SPOT®.TBj
Total cholesterol
PPD (local testing)
Low-density lipoprotein
High-density lipoprotein
Triglycerides
Abbreviations: eGFR = estimated glomerular filtration rate; FSH = follicle-stimulating hormone; HBV = hepatitis B 
virus; PPD = purified protein derivative; RBC = red blood cell; TB = tuberculosis; 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
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.
d
Microscopic examination of sediment performed only if abnormalities are noted on the routine urinalysis.

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e
eGFR for serum creatinine calculated by the central laboratory using the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) Creatinine 2009 equation.
f
Test required at Visit 1 only to determine eligibility of patient for the study.
g
A positive hepatitis C antibody (Hep C antibody) result will be confirmed with an alternate hepatitis C method.
h
For all women of childbearing potential, a serum pregnancy test will be performed at Visit 1 and a local urine 
pregnancy test will be performed at Visit 2 and at all subsequent study visits after Visit 3.  If required per local 
regulations and/or institutional guidelines, pregnancy testing can occur at other times during the study treatment 
period.
i
To confirm postmenopausal status for women ≥40 and <60 years of age who have had a cessation of menses, an
FSH test will be performed. Nonchildbearing potential is defined as an FSH ≥40 mIU/mL and a cessation of
menses for at least 12 months.
j
The QuantiFERON®-TB Gold test is the preferred alternative to the PPD test for the evaluation of TB infection,
and it may be used instead of the PPD test or T-SPOT®.TB test and may be read locally. If the 
QuantiFERON®-TB Gold test is indeterminate, 1 retest is allowed.  If the retest is indeterminate, then the patient 
is excluded from the study.
k
HBV DNA testing will be done in those patients who are HBcAb+ at screening.

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

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
informed consent form

other relevant documents (for example, curricula vitae, advertisements)
Appendix 3.1.4.
Regulatory Considerations
This study will be conducted in accordance with the protocol and with the:

consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third party.
Appendix 3.1.5.
Investigator Information
Physicians with a specialty in dermatology will participate as investigators in this clinical trial.
Appendix 3.1.6.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.7.
Final Report Signature
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

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
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
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 those 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.

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Appendix 3.3.
Study and Site Closure
Appendix 3.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly, 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. 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.   
Appendix 3.4.
Publication Policy
The publication policy for Study I4V-MC-JAIN is described in the Clinical Trial Agreement.

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

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Appendix 5.
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 9.4.10
Section 9.4.10
Section 8.1.1
Section 8.1.2
ALT/ AST
≥2x ULN
ALT ≥3x ULN
(ALT only)
ALT ≥5x ULN on 
≥2 consecutive 
tests (ALT only)
≥5x ULN

>8x ULN

>5x ULN for >2 weeks

>3x ULN AND TBL 
>2x ULN or INR >1.5

>3x ULN with 
symptomsa
ALP
≥2x ULN
≥2x ULN
≥2x ULN on ≥2 
consecutive tests
No applicable 
criteria

>3x ULN

>2.5x ULN AND TBL 
>2x ULN 

>2.5x ULN with 
symptomsa
TBL
≥1.5x ULN
≥2x ULN
≥2x ULN 
(excluding 
Gilbert’s 
syndrome)
No applicable 
criteria

ALT or AST >3x ULN 
AND TBL >2x ULN

ALP >2.5x ULN AND 
TBL >2x 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.
American Academy of Dermatology:  Criteria 
for the Diagnosis and Assessment of Atopic Dermatitis
Features to be considered in diagnosis of patients with atopic dermatitis:
Essential Features—Must be present:

pruritus

eczema (acute, subacute, chronic)
o
typical morphology and age-specific patterns*
o
chronic or relapsing history
*Patterns include the following:
1)facial, neck, and extensor involvement in infants and children
2)current or previous flexural lesions in any age group
3)sparing of the groin and axillary regions
Important Features—Seen in most cases, adding support to the diagnosis:

early age of onset

atopy
o
personal and/or family history
o
Immunoglobulin E reactivity

xerosis
Associated Features—These clinical associations help to suggest the diagnosis of atopic dermatitis 
but are too nonspecific to be used for defining or detecting atopic dermatitis for research and 
epidemiologic studies:

atypical vascular responses (e.g., facial pallor, white dermographism, delayed blanch response)

keratosis pilaris/pityriasis alba/hyperlinear palms/ichthyosis

ocular/periorbital changes

other regional findings (e.g., perioral changes/periauricular lesions)

perifollicular accentuation/lichenification/prurigo lesions
Exclusionary Features—It should be noted that a diagnosis of atopic dermatitis depends on 
excluding conditions, such as:

scabies

seborrheic dermatitis

contact dermatitis (irritant or allergic)

ichthyoses

cutaneous T-cell lymphoma

psoriasis

photosensitivity dermatoses

immune deficiency diseases

erythroderma of other causes
Source: Eichenfield et al. (2014).

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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.
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; fXa = factor Xa; 
MTHFR = methylene tetrahydrofolate reductase; PT = prothrombin time; PTT = partial thromboplastin time.

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Appendix 9.
Protocol Amendment I4V-MC-JAIN(e) 
Summary 
A Phase 3, Multicenter, Double-Blind, Randomized, 
Placebo-Controlled Study Evaluating the Safety and 
Efficacy of Baricitinib in Combination with Topical 
Corticosteroids in Adult Patients with 
Moderate-to-Severe Atopic Dermatitis Who Have 
Experienced Failure to Cyclosporine or Are Intolerant to, 
or Have Contraindication to, Cyclosporine
Overview
Protocol I4V-MC-JAIN(d) has been amended. This amendment is substantial based on the 
criteria set forth in Article 10(a) of Directive 2001/20EC of the European Parliament and the 
council of the European Union. The new protocol is indicated by amendment (e) and will be 
used to conduct the study in place of any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are described in the table 
below.  In addition, minor typographical corrections not affecting the content have been made in 
the document.

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Amendment Summary for Protocol I4V-MC-JAIN Amendment (e)
Section # and Name
Description of Change
Brief Rationale
Section 1 
A bridging extension period was added between the 
Long-Term Extension (Period 3) and the Post-
Treatment Follow-Up Period (Period 4). The Post-
Treatment Follow-Up Period was renamed 
Period 5.
The Bridging extension period will allow for 
additional long-term safety information on the IP to 
be collected and will provide to study participants
the opportunity to continue study treatment until 
commercial availability of baricitinib in this 
indication in the respective countries or for a 
maximum of 96 additional weeks.
Section 1 and Section 10.3 1 
Text was added to provide additional detail of the 
logistic regression analysis.
Text was added to clarify that baseline disease 
severity would be assessed via investigator’s global 
assessment and that baseline score will also be 
included in the model.
Section 2 - Table JAIN.1.
Included an additional six visits to reflect the 
bridging extension period.
Added collection of PGI-S-AD up to Week 68.
Updated to reflect the extension of the duration of 
the trial by approximately two years (up to 
Week 200).
To align with the collection of the other PROs on 
the ediaries.
Section 4 – Table JAIN.2.
Exploratory efficacy analysis wording was added to 
the Exploratory Endpoints section.
Updated to indicate that additional efficacy 
analyses may be performed beyond Week 104.
Section 5.1 and Figure JAIN.1.
Reflected the addition of the bridging extension 
period (now Period 4).
Figure JAIN.1 was updated to include the 
additional period.
Updated to reflect the extension of the duration of 
the trial by approximately two years (up to 
Week 200).
Section 5.1.4 
Replaced by the design details of the Bridging 
Extension Period. 
The Post-Treatment Follow-Up Period design 
details are now presented in Section 5.1.5.
Text was added to clarify that treatments received 
during Period 4 are essentially a continuation of the 
treatment options available in treatment Period 3. 

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Section 5.4
Text was added to provide rationale for the bridging 
extension period.
Specified that Background TCS will be assigned 
until Week 104. 
Period 4 will give to patients who have completed 
Week 104 visit and have not met criteria for 
permanent discontinuation the possibility to remain 
in the trial for a maximum of 96 additional weeks 
(up to Week 200). This will provide additional long 
term efficacy and safety information.
The requirement for concomitant background  TCS 
is limited to Period 2 and 3. During Period 4, 
concomitant use of TCS may be continued, as 
directed by the investigator, as per clinical practice.
Section 7.2, Section 7.6, and Section 7.7.3 
Visit, Week, and Period numbers were updated to 
be consistent with the additional visits (additional 
period).
To reflect the extension of the treatment period 
with the addition of Period 4 (Bridging extension).
Section 7.7.1
Updated language specifying which periods 
medications and procedures referred to and added 
text to specify that, during Period 4, concomitant 
use of TCS may be continued, as directed by the 
investigator, as per clinical practice.
Updated to clarify the requirement and resctrictions 
relative to the use of emollient and TCS during the 
different Periods.
Section 7.7.2 
Specified that in Period 4, use of concomitant TCS 
may be continued as directed by the investigator.
In Period 4, TCS use is allowed as directed by the 
investigator and TCS will not be provided by the 
sponsor.
Section 7.7.4 
Removed allergen immunotherapy from prohibited 
procedures
Due to the extended duration of the study, the 
sponsor anticipates some patients may require 
allergen immunotherapy for allergic conditions.
Section 7.7.5.2 
Clarified that the same rules for the management of 
rescue therapy in Period 3 will apply to Period 4.
Patients in Period 4 will have the same possibility 
of rescue therapies as in Period 3.
Section 7.8 
Detailed objectives of Period 4 and conditions 
underwhich patients can enter Period 4.
The trial duration is increased for up to 96 
additional weeks to give to patients the possibility 
to remain in the trial until baricitinib is approved 
for the treatment of AD and becomes reimbursed or 
a negative regulatory opinion is received. 

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Section 8.1.1 - Table JAIN.4. 
Removed wording allowing to resume IP after 
institution of appropriate treatment of a first VTE.
Permanent discontinuation of IP is required after 
occuance of any VTE in the study.
Section 8.1.2 
Specified that patients will be discontinued from 
investigational product if a VTE develops and 
added a note regarding followup testing.
Permanent discontinuation of IP is required after 
occurance of any VTE in the study.
Section 8.2 
Specified that the study may be terminated in a 
specific country after baricitinib is approved for the 
treatment of AD and becomes reimbursed or a 
negative regulatory opinion is received in that 
country.
To align with the objectives of the extension of the 
duration of the trial.
Section 9.4.8 
Clarified the existing wording concerning the
periodic monitoring of HBV DNA for patients who 
are HBc Antibody positive at Screening which is 
described in the SOA. 
To correct the discrepancy between section 9.4.8 
and the SOA table. 
Section 10.3.7.4 
Section created to clarify that other interim analyses 
may be conducted to support regulatory 
submissions and scientific disclosures.
To align with regulatory submissions and 
disclosures plans.
Appendix 3.3.2 
Wording was added to clarify that the study may be 
terminated 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. 
To align with the objectives of the extension of the 
duration of the trial.

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

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1.
Synopsis
…
Summary of Study Design:
Study I4V-MC-JAIN (JAIN) is a Phase 3, multicenter, double-blind, randomized, 
placebo-controlled study evaluating the safety and efficacy of baricitinib 1-mg once daily (QD), 
2-mg QD, and 4-mg QD compared with placebo in patients with moderate-to-severe AD who are 
receiving background topical corticosteroid (TCS) treatment and who have experienced failure to 
cyclosporine or are intolerant to, or have a contraindication to, cyclosporine.
The study consists of 54 periods:
Period 1: Screening Period (Visit 1), up to 5 weeks prior to randomization
Period 2: 52-week Double-Blind Treatment Period: from Week 0 (Baseline; Visit 2) up 
to Week 52 (Visit 14)
Period 3: 52-week Double-Blind, Long-Term Extension Period: from Week 52 
(Visit 14) to Week 104 (Visit 22)
d. Randomized Down-Titration Substudy (Week 52)
Responders who are eligible to enter the substudy will be rerandomized as 
follows:
baricitinib 4-mg treatment group 1:1 to baricitinib 2-mg, or baricitinib 
4-mg.
baricitinib 2-mg treatment group 1:1 to baricitinib 1-mg, or baricitinib 
2-mg.
e.
Responders who are not eligible to enter the randomized downtitration will 
continue on the treatment regimen assigned at baseline; however, rerandomization 
to either 4-mg or 2-mg baricitinib is available for the placebo, baricitinib 2-mg, 
and 1-mg treatment groups if patients have a worsening of symptoms.
f.
Nonresponders in the placebo, baricitinib 2-mg, or baricitinib 1-mg treatment 
groups will be rerandomized at a 1:1 ratio to baricitinib 4-mg or baricitinib 2-mg 
QD at Week 52.  After rerandomization, patients will remain on the same dose of 
baricitinib for the remainder of the study.  Nonresponders who were randomized 
to baricitinib 4-mg will remain on 4-mg.
Period 4: Bridging Extension: from Week 104 (Visit 22) and up to Week 200 (Visit 28). 
Subjects who have completed Week 104 and have not met criteria of permanent 
discontinuation will have the possibility to remain in the trial for up to 96 
additional weeks (up to Week 200).
Period 45: Post-Treatment Follow-Up Period: from last treatment period visit or early 
termination visit (ETV) to 4 weeks after the last dose of investigational product.

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Treatment Arms and Duration:
At baseline, patients will be randomized at a 1:1:2:1 ratio to receive placebo QD, baricitinib 
1-mg QD, baricitinib 2-mg QD, or baricitinib 4-mg QD for up to 104200 weeks.
…
Statistical Analysis
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the 
intent-to-treat population and safety analyses will be conducted on those patients who receive at 
least 1 dose of investigational product.
Treatment comparisons of discrete efficacy variables will be made using a logistic regression 
analysis with treatment and, baseline disease severity (vIGA AD) and baseline score in the 
model.  Region may be added to the model if patient numbers allow.  The proportions and 95% 
confidence interval (CI) for the treatment comparisons will be reported.  If a patient needs to use 
rescue medication, the data from that point forward will be considered missing and missing data 
will be imputed using the nonresponder imputation (NRI) method.  Additional analyses will be
conducted using all observed data regardless of whether rescue medication was used or not.
Treatment comparisons of continuous efficacy and health outcome variables will be made using 
mixed-effects models for repeated measures (MMRM) model with treatment, baseline severity
(vIGA AD), visit, and treatment-by-visit interaction as fixed categorical effects and baseline 
score and baseline score-by-visit interaction as fixed continuous effects. Region may be added 
to the model if patient numbers allow.  An unstructured covariance matrix will be used to model 
the within-patient variance–covariance errors.  Type III sums of squares for the least squares 
means (LSMs) will be used for the statistical comparison and contrasts will be set up within the 
model to compare treatment groups at specific time points of interest.

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2.
Schedule of Activities
Table JAIN.1.
Schedule of Activities
Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/ 
ETa
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
10820
4
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
Inclusion and 
exclusion review
X
X
Informed consent
X
Clinical 
Assessments
Demographics
X
Medical history
X
Substance Use 
(alcohol, tobacco)
X
Previous and current 
AD treatments
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Vital signs (BP and 
Pulse)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical 
examination
X
Symptom-directed 
physical 
examinationb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG 
(single)
X
Chest x-rayc
(posterior–anterior 
view)
X
TB testd
X
Read PPD if 
applicable (48 to 72 
Xe

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Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/ 
ETa
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
10820
4
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
hours after PPD)
Pre-existing 
Conditions
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO (patient diary) 
dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ePRO (patient diary) 
returned
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Randomization/
rerandomizationg
X
Xg
IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP Dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP Returned and 
Compliance 
Assessed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weigh and dispense 
background TCS 
(tubes with cap)q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weigh and record 
returned background 
TCS (tubes with 
cap)q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Scales
IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAIN(e) Clinical Protocol
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Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/ 
ETa
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
10820
4
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
Health Outcomes 
Measures and 
Other 
Questionnairesh
Itch NRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
Skin Pain NRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
ADSS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
Xf
PGI-S-AD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xf
POEM
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HADS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
EQ-5D-5L
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
WPAI-AD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
SF-36
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
C-SSRS and Self-
Harm Supplementi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-
Up Formj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory 
Assessments
Lipids (Fasting 
Visit)k
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical Chemistryl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum Pregnancym
X
FSHn
X
TSH
X

I4V-MC-JAIN(e) Clinical Protocol
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Period 1:  
Screening
Period 2:  Double-blind Treatment Period
Period 3:  Long-Term Extension
Period 4:  Bridging Extension PTFU
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/ 
ETa
23
24
25
26
27
28/ 
ETa
801a
Weeks from 
Randomization
-8 to -35 
days
0
1
2
4
8
12 16 20
24
32
40
48
52
56
60
64
68
76
84
92
104
120 136 152 168 184
200
10820
4
Visit tolerance 
interval (days)
0
±2 ±2 ±2 ±2 ±4 ±4 ±4
±5
±5
±5
±5
±5
±4
±4
±4
±4
±5
±5
±5
±5
±7
±7
±7
±7
±7
±7
28±4
HIV
X
HCV Antibodyo
X
HBV testing
X
HBV DNAp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xr
Xr
Urine Pregnancym
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacogenetics:  
blood
X
X
Serum 
immunoglobulin 
(IgE)
X
X
X
X
X
X
X
Xr
Exploratory storage 
samples (serum and 
plasma)
X
X
X
X
X
X
X
Xr
RNA and 
biomarkers:  blood
X
X
X
X
X
X
X
Xr
Abbreviations: AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BP = blood pressure; C-SSRS = Columbia Suicide Severity Rating Scale 11 
categories suicidal ideation/suicidal behavior; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and Severity Index; ECG = electrocardiogram; 
EQ-5D-5L = the European Quality of Life–5 Dimensions 5 Levels; ET = early termination; ePRO = electronic patient-reported outcomes (device); 
FSH =  follicle-stimulating hormone; HADS = Hospital Anxiety Depression Scale; HCV = hepatitis C virus; HBV = hepatitis B virus; HIV = human 
immunodeficiency virus; ICF = informed consent form; IGA = Investigator’s Global Assessment; IgE = immunoglobulin E; IP = investigational product; 
IWRS = interactive web-response system; NRS = Numeric Rating Scale; PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; 
POEM = Patient-Oriented Eczema Measure; PPD = purified protein derivative; PTFU = post-treatment follow-up; SF-36 =Medical Outcomes Study 36-item 
short-form health survey; SCORAD = SCORing Atopic Dermatitis; TB = tuberculosis; TCS = topical corticosteroids; TSH = thyroid-stimulating hormone; 
V = visit; WPAI-AD = Work Productivity and Activity Impairment-Atopic Dermatitis.

I4V-MC-JAIN(e) Clinical Protocol
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a
An early termination visit should be conducted if patient discontinues from the study before Week 104200. Visit 801 is the post-treatment follow-up visit, 
which occurs after the patient has been off baricitinib/study drug 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 2228/ET; Visit 801 (follow-up visit) is not required.  ET visit activities do not need to be 
duplicated if occurring at the time of a scheduled visit. 
b
The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints.
c
A posterior–anterior chest x-ray will be performed at screening unless one has been performed within the past 6 months and the x-ray and reports are 
available.
d
TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®. See Exclusion Criterion [40] for description of TB testing. In countries where the 
QuantiFERON-TB Gold test or T-SPOT is available, either test may be used instead of the PPD TB test. The QuantiFERON-TB Gold test may be performed 
locally or centrally; the T-SPOT must be performed locally. (Note: Exception: Patients with a history of active or latent TB who have documented evidence 
of appropriate treatment, have no history of re-exposure since their treatment was completed, and have a screening chest x-ray with no evidence of active TB 
may be enrolled if other entry criteria are met. Such patients would not be required to undergo the protocol-specific TB testing but must have a chest x-ray at 
screening.)
e
If PPD testing was chosen to test for TB, then the patient must return and PPD test read 48 to 72 hours after Visit 1 (post-PPD).
f
Applies to ET Visit if conducted prior to Week 68 only.
g
At Week 52, patients who are eligible for the randomized downtitration substudy and nonresponders will be rerandomized as described in Section 5.1.3. 
h
The following measures (Itch NRS, Skin Pain NRS, ADSS, PGI-S-AD, POEM, DLQI, HADS, EQ-5D-5L, WPAI-AD, SF-36) should be completed prior to 
any clinical assessments being performed on days when study visits occur.
i
Suicidal ideation and behavior subscales excerpt – Adapted for the assessment of 11 preferred ideation and behavior categories.
j
The Self-Harm Follow-Up Form is required only if triggered by the Self-Harm Supplement Form.
k
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.
l
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).
m For all women of childbearing potential, a serum pregnancy test (central laboratory) will be performed at Visit 1.  Urine pregnancy tests (local laboratory) will 
be performed at Visit 2 and at all subsequent study visits after Visit 3.  If required per local regulations and/or institutional guidelines, pregnancy testing can 
occur at other times during the study treatment period.
n
For female patients ≥40 and <60 years of age who have had a cessation of menses for at least 12 months, an FSH test will be performed to confirm 
nonchildbearing potential (FSH ≥40 mIU/mL).
o
For patients who are positive for HCV antibody, a follow-up test for HCV RNA will be performed automatically.  Patients who are positive for HCV antibody 
and negative for HCV RNA may be enrolled.
p
Patients who are positive for HBcAb and negative for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive, regardless of HBsAb status 
or level, must undergo HBV DNA testing per the schedule.
q Beyond Week 104, low and mid potency TCS will no longer be provided by the sponsor.
r
Only applicable to ET visits and V801 before Period 4.

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NOTE:  Patients completing V22 and planning to sign the ICF for amendment (e) can participate as long as they have not completed 
a V801.

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4.0.
Objectives and Endpoints
Table JAIN.2.
Objectives and Endpoints
…
Exploratory Endpoints 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, DLQI, WPAI-AD, EQ-5D-5L, Itch NRS, ADSS Item 1, 2, 
3 scores, Skin Pain NRS, SF-36, PGI-S-AD.  Patients continuing on placebo as responders will be assessed during 
the long-term extension for relevant efficacy endpoints.  Assessments of efficacy may be performed beyond 
Week 104 up to Week 200.  The timing of the data lock(s) for the analysis of the efficacy data from the randomized 
withdrawal sub-study will be determined by the retreatment rates (see Section 10.3.7).
…
5.1.
Overall Design
Study I4V-MC-JAIN (JAIN) is a Phase 3, multicenter, double-blind, randomized, 
placebo-controlled study evaluating the safety and efficacy of baricitinib 1-mg QD, 2-mg QD,
and 4-mg QD in combination with TCS in patients with moderate-to-severe atopic dermatitis
(AD) who have experienced failure of cyclosporine, or are intolerant to, or have a 
contraindication to, cyclosporine. The study is divided into 45 periods:  a 5-week Screening 
period, a 1-year Double-Blind Treatment period (Week 0 through Week 52), a 1-year double-
blind, long-term extension (Week 52 through Week 104) that includes a randomized 
downtitration substudy, a bridging extension that may last up to 96 weeks (Week 104 to up to 
Week 200) and a 4-week Post-Treatment Follow-Up period.
…

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Abbreviations:  AD = atopic dermatitis; eGFR = estimated glomerular filtration rate;
ET = early termination; IGA = Investigator’s Global Assessment; IP = investigational 
product; PPD = purified protein derivative; QD = once daily; TB = tuberculosis; TCS = 
topical corticosteroids; V = visit; W = week.
a
Applicable to patients taking topical treatments (excluding emollients) or 
systemic treatments for AD at the time of screening.
b
Maximum dose of baricitinib for patients with renal impairment (defined as 
eGFR <60 mL/min/1.73 m2) will be 2-mg QD.
c
Patients for whom PPD skin test for the evaluation of TB infection was 
performed at V1 must return and PPD test must be read 48 to 72 hours after Visit 1 
(post-PPD).
d
At Visit 2 (W0) and up to Visit 22 (W104), patients will be supplied with mild-
and moderate-potency TCS to be applied per the guidelines in Section 7.7.2.
e
At Week 52, responders (IGA 0 or 1) and partial responders (IGA 2) who were 
assigned to baricitinib 4-mg or 2-mg, at randomization, are currently receiving 
investigational product (does not currently have study drug interrupted), and have not 
used high- or ultra-high-potency TCS in the previous 14 days will be enrolled into the 
downtitration substudy. If a patient in the substudy has an IGA ≥3 during Periods 3 or 
4, they will be retreated automatically with their presubstudy baricitinib dose for the 
remainder of the study.
f
At Week 52, responders (IGA 0 or 1) and partial responders (IGA 2) in the 
baricitinib 4-mg or baricitinib 2-mg treatment groups who are not eligible for the 
randomized downtitration substudy and those who are in the baricitinib 1-mg or 
placebo groups will remain on their current dose of investigational product.  If 
worsening of AD symptoms occurs any time during Periods 3 or 4thereafter such that a 
patient’s IGA is ≥3, with the exception of patients in the baricitinib 4-mg group, they 
will be rerandomized automatically at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 
4-mg QD.  Rerandomization will only occur once. Patients in the baricitinib 4-mg 
group will remain on 4-mg.
g
Beginning at Visit 14 (Week 52), nonresponders (IGA ≥3) in the placebo, 
baricitinib 1-mg or baricitinib 2-mg treatment groups will be rerandomized at a 1:1 
ratio to baricitinib 4-mg or baricitinib 2-mg QD. Nonresponders randomized to 
baricitinib 4-mg at baseline will remain on 4-mg.  After rerandomization, patients will 
remain on the same dose of baricitinib for the remainder of the study.
h
Occurs approximately 28 days after the last dose of IP. Not required for patients 
who have been off drug for 28 days or more at the time of their last visit.
Figure JAIN.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIN.
…
5.1.4
Period 4: Bridging Extension
Patients who have completed Week 104 and have not met criteria for permanent discontinuation 
will have the possibility to remain in the trial for up to 96 additional weeks (up to Week 200). 
During Period 4, patients will continue to receive the same treatment (baricitinib or placebo) they 
received during Period 3, and will have the same options for dose changes as Period 3 (if not 
already implemented in Period 3):

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
Randomized Down titration substudy: the substudy will continue during Period 4. 
Therefore, patients who have not met the criterion for retreatment in Period 3 will have 
the possibility to be retreated with the baricitinib dose they received prior to the substudy 
if worsening of AD symptoms occurs such that IGA increases to ≥3. 

Patients with an IGA 0, 1, or 2 at Week 52 and who were not eligible to the randomized 
downtitration, will be rerandomized at a 1:1 ratio to baricitinib 2-mg QD or baricitinib 
4-mg QD if they experience a worsening of symptoms of AD such that IGA increases to
≥3, unless the randomized uptitration has already occurred in Period 3. Patients in the 
baricitinib 4-mg group will remain on 4-mg.

Patients with an IGA 0, 1, or 2 at Week 52 and who were not eligible to the randomized 
downtitration, will be rerandomized at a 1:1 ratio to baricitinib 2 mg QD or baricitinib 
4-mg QD if they experience a worsening of symptoms of AD such that IGA increases to 
≥3, unless the randomized uptitration has already occurred in Period 3.  Patients in the 
baricitinib 4 mg group will remain on 4 mg.
5.1.45.1.5
Period 45:  Post Treatment Follow-Up
Patients who complete the study through Week 104200 will have a post-treatment follow-up visit 
(Visit 801) approximately 28 days after the last dose of investigational product.
…
5.4.
Scientific Rationale for Study Design
…
All patients in Study JAIN will be assigned investigational product with concomitant mild- to 
moderate-potency TCS until Week 104 (Visit 22) and investigators may rescue patients who are 
experiencing unacceptable or worsening symptoms of AD with high- or ultra-high-potency TCS.  
(See Section 7.7.5 for all rescue options). 
Topical rescue treatments (as outlined in Section 7.7.5) will be available during Study JAIN to 
facilitate the management of disease, as there are instances where patients will remain on the 
same dose of baricitinib during episodes of worsening.
The 16-week efficacy endpoint was chosen because it is likely that a robust clinical effect will be 
observed with baricitinib within this timeframe based on the Phase 2 study results in AD, and for 
consistency with other studies in AD. This timing will allow adequate duration on a stable dose 
of baricitinib to assess the benefit/risk profile of the dose regimens.
During the long-term extension (Period 3), eligible patients will participate in a downtitration 
substudy.  The objective of the substudy is to evaluate the possibility of maintaining efficacy 
with a lower dose of baricitinib in patients with response (IGA 0 or 1) or partial response 
(IGA 2) to baricitinib 2-mg QD or 4-mg QD in combination with TCS.
Period 4 will provide patients who have completed Week 104 visit and have not met criteria for 
permanent discontinuation, the possibility to remain in the trial for up to 96 additional weeks (up 
to Week 200). This will allow for additional long-term efficacy and safety information to be 

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collected, and provide patients the opportunity to continue study treatment until the anticipated 
approval of baricitinib in this indication.
The Post-Treatment Follow-Up Period (Period 45) is for safety monitoring after the patient has 
been off investigational product for approximately 28 days.
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized in a 1:1:2:1 ratio to receive 
placebo QD, baricitinib 1-mg QD, 2-mg QD, or 4-mg QD to double-blind treatment at Visit 2
(Week 0).  Randomization will be stratified by geographic region if the planned country 
allocation justifies, and disease severity at baseline (IGA 3 versus 4). Assignment to treatment 
groups will be determined by a computer-generated random sequence using an IWRS.  The 
IWRS will be used to assign cartons, each containing 4 blister packs of double-blind 
investigational product tablets to each patient, starting at Visit 2 (Week 0), and at each visit up to 
and including Visit 2228 (Week 104200).  Site personnel will confirm that they have located the 
correct carton by entering a confirmation number found on the carton into the IWRS.
7.6.
Treatment Compliance
Patient compliance with study medication will be assessed at each visit during the treatment 
period (Visit 4 through Visit 2228) by counting returned tablets.
7.7.1. 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 up to Week 104.  After 
Week 104, the continued use of emollients is encouraged.  Moisturizers with 
antipruritics or antiseptics are not permitted up to Week 104.  If daily applications are 
missed, it will not be considered a protocol violation.  Emollients will not be supplied by 
the sponsor, unless required by local regulations.
o
Patients should not apply emollients on the day of their study visit prior to the 
procedures to allow for adequate assessment of skin dryness.

Background TCS therapy (e.g., triamcinolone 0.1% cream and/or hydrocortisone 2.5% 
ointment) are to be used on active lesions in Periods 2 and 3, as described in 
Section 7.7.2.

During Periods 2 and 3, hHigh- or ultra-high-potency TCS are only permitted as rescue 
therapy as described in Section 7.7.5 (Rescue Therapy).

During Period 4, concomitant use of TCS may be continued, as directed by the 
investigator, as per clinical practice. 

TCIs (e.g., tacrolimus and pimecrolimus), or topical PDE-4 inhibitor (i.e., crisaborole,
where approved) are permitted in place of TCS on areas where application of TCS is 
considered inappropriate by the investigator; use should be limited to problem areas 
(e.g., face, neck, skin folds, genital areas, etc.) as described in Section 7.7.2.

Phototherapy, including therapeutic phototherapy (psoralen and ultraviolet A, 
ultraviolet B, excimer laser), is permitted as rescue therapy in Periods 2 or 3to 4 (see 

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Section 7.7.5, Rescue Therapy); however, it requires a temporary interruption of 
investigational product (see Section 8.1.1).
…
7.7.2. Use of Topical Corticosteroids
A washout period of 14 days is required for all TCS prior to randomization at Visit 2.
At baseline (Week 0, Visit 2) and up to Week 104 (Visit 22), patients will receive triamcinolone 
0.1% cream (or equivalent-potency TCS) and hydrocortisone 2.5% ointment (or 
equivalent-potency TCS)…
After Week 104, use of TCS may be continued as directed by the investigator, as per clinical 
practice.  Background TCS will no longer be provided nor reimbursed to study participants by the 
sponsor, unless required by local law. 
Choice of Background Topical Corticosteroid
Where possible, triamcinolone cream 0.1% and/or hydrocortisone 2.5% ointment will be 
supplied by the sponsor for use as background TCS up to Week 104 (Visit 22).  In the event of 
these specific TCS being unavailable, an alternate, equivalent-potency TCS may be provided by 
the sponsor (see below).  Topical corticosteroid use, when supplied by the sponsor, should be 
recorded via weight of dispensed and returned tubes as indicated in the Schedule of Activities 
(Section 2). In the event that the sponsor is unable to supply TCS, commercially available 
triamcinolone 0.1% cream and/or hydrocortisone 2.5% ointment may be supplied by the sites.  
7.7.3. Use of Antihistamines
…
During Periods 3, and 4, and 5, there are no restrictions for antihistamine use; both sedating and 
nonsedating antihistamines are permitted.
7.7.4. Prohibited Medications and Procedures
Prohibited Medications and Procedures Not Requiring Urgent 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, the prohibited therapy must be discontinued.  If the patient is not able 
to discontinue use of the following then investigational product will be permanently
discontinued.

topical antihistamines or sedating, systemic antihistamines in Period 2 (see Section 7.7.3,
Use of Antihistamines, for additional information).

allergen immunotherapy

self-treatment with tanning booth

bleach baths (swimming in chlorinated pools is permitted)

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7.7.5.2.
Rescue during Periods 3 and 4:  from Week 52 (Visit 14) to Week 104 200
(Visit 2228)
In Period 3, all patients entering Period 3 will continue to use concomitant background TCS
(e.g., triamcinolone 0.1% cream and hydrocortisone 2.5% ointment) as described in Section 7.7.
In Period 4, use of concomitant may continue as directed by the investigator, as per clinical 
practice.  All patients andmay be rescued at any time with high- or ultra-high-potency TCS or 
phototherapy as described in Section 7.7.
As mentioned in Sections 5.1.3, and 5.1.4, patients who reach an IGA ≥3 after entry into the 
randomized downtitration substudy will be automatically retreated with their presubstudy dose of 
baricitinib.
…
7.8.
Treatment after the End of the Study
Period 4 will provide patients who have completed Week 104 visit and have not met criteria for 
permanent discontinuation, the possibility to remain in the trial for up to 96 additional weeks (up 
to Week 200) and thus provide patients the opportunity to continue study treatment until the 
anticipated approval of baricitinib in this indication.
After the conclusion of the study, continued access to baricitinib will not be provided.  Patients 
will be referred to their local treatment centers for AD therapy as clinically indicated.
8.1.1. Temporary Interruption of Investigational Product
…
Table JAIN.4.
Medical and Laboratory Criteria for Temporary Interruption of 
Investigational Product
Hold Investigational Product if the Following 
Laboratory Test Results or Clinical Events Occur
Investigational Product May Be Resumed When
WBC count <2000 cells/L
(<2.00x103/L or <2.00 GI/L)
WBC count 2500 cells/L
(≥2.50x103/L or ≥2.50 GI/L)
ANC <1000 cells/L
(<1.00x103/L or <1.00 GI/L)
ANC ≥1200 cells/L
(≥1.20x103/L or ≥1.20 GI/L)
Lymphocyte count <500 cells/L
(<0.50x103/L or <0.50 GI/L)
Lymphocyte count 750 cells/L
(≥0.75x103/L or ≥0.75 GI/L)
Platelet count <75,000/L
(<75x103/L or <75 GI/L)
Platelet count 100,000/L
(≥100x103/L or ≥100 GI/L)
eGFR <40 mL/min/1.73 m2 (from serum creatinine) for 
patients with screening eGFR ≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 (from serum creatinine) for 
patients with screening eGFR ≥40 to <60 mL/min/1.73 m2
eGFR 40 mL/min/1.73 m2
ALT or AST >5 x ULN
ALT and AST return to <2 x ULN, and IP is not 

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considered to be the cause of enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 10 g/dL (≥100.0 g/L)
Symptomatic herpes zoster
All skin lesions have crusted and are resolving
Infection that, in the opinion of the investigator, merits the 
IP being interrupted
Resolution of infection
Clinical features of VTE (such as deep vein thrombosis  or 
pulmonary embolism) are presenta
After evaluation and institution of appropriate 
treatment of VTEb
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; VTE = venous thromboembolic event; WBC = white blood cell.
a
Evaluate promptly and institute appropriate treatment.  If upon evaluation VTE is ruled out and no other 
temporary interruption or permanent discontinuation criteria are met, then IP may be resumed.
b
If after evaluation and institution of appropriate treatment the investigator deems that the patient is still at 
significant risk, or if this would constitute a second VTE for the patient, then IP should be discontinued 
permanently.
…
8.1.2. Permanent Discontinuation from Investigational Product
…
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)

hepatitis B virus DNA is detected with a value above limit of quantitation or 2 sequential 
tests return a value of below the limit of quantitation (see Section 9.4.8).

confirmed second VTE 

certain prohibited medications are taken per Section 7.7.4, Prohibited Medications and 
Procedures.

development of a VTE
Note: Patients who develop a VTE may have additional follow up and testing recommended 
(see Appendix 8).
…
8.2.
Discontinuation from the Study
Patients will be discontinued in the following circumstances:
…

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.
…

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9.4.8. Hepatitis B Virus DNA Monitoring
Patients who are HBcAb positive and HBV DNA negative (undetectable) at Visit 1 will require 
periodic measurement of HBV DNA ast per study schedule (Section 2) Week 16 (Visit 8) or 
ETV, regardless of their hepatitis B surface antibody (HBsAb) status.
10.3.1. General Statistical Considerations
…
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated.  Treatment comparisons of discrete efficacy variables between baricitinib and placebo 
will be made using a logistic regression analysis with baseline disease severity (vIGA AD), 
baseline score and treatment group in the model.  Region may be added as an additional factor if 
the planned country allocation justifies, and stratification has not resulted in empty strata. This 
will be finalized in the SAP. If appropriate, treatment-by-region interaction may be added to the 
model of the primary and key secondary variables as a sensitivity analysis. If this interaction is 
significant at a 2-sided 0.1 level, further inspection will be used to assess whether the interaction 
is quantitative (i.e., the treatment effect is consistent in direction but not size of the effect) or 
qualitative (the treatment is beneficial for some but not all regions).  The percentages, difference 
in percentages, and 95% confidence interval (CI) of the difference in percentages will be 
reported.  The p-value from the Fisher exact test will also be produced.  Additional relative 
measures, for example, odds ratio, may be reported as appropriate.
When evaluating continuous measures over time, a restricted maximum likelihood-based mixed 
model for repeated measures (MMRM) will be used.  The model will include treatment, baseline 
severity (vIGA AD), visit, and treatment-by-visit interaction as fixed categorical effects and 
baseline score and baseline score-by-visit interaction as fixed continuous effects.  Region may be 
added as an additional factor if the planned country allocation justifies. An unstructured 
(co)variance structure will be used to model the between- and within-patient errors.  If this 
analysis fails to converge, other structures will be tested.  The Kenward–Roger method will be 
used to estimate the degrees of freedom.  Type III sums of squares for the least squares means 
(LSMs) will be used for the statistical comparison; 95% CI will also be reported.  Contrasts will 
be set up within the model to test treatment groups at specific time points of interest.  Further 
details on the use of MMRM will be described in the SAP.
…
10.3.7.4  Other Interim Analyses
Besides DMC members and Unblinded Study Team for the Primary Analyses for Regulatory 
Submission, a limited number of pre-identified individuals may gain access to the limited 
unblinded data, as specified in the unblinding plan, prior to the primary analysis or final database 
lock for preparation of regulatory documents.  Interim locks will be conducted at various 
timepoints to support regulatory submissions and scientific disclosures.  The timing of the data 
lock(s) for the analysis of the efficacy data from the sub-study will be determined by the 

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retreatment rates. Information that may unblind the study during the analyses will not be 
reported to study sites or blinded study team until the study has been unblinded.
Unblinding details will be specified in a separate unblinding plan document to ensure proper 
firewalls between the unblinded study team and study sites.
…
Appendix 3.3.
Study and Site Closure
…
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.  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.   

PPD
Leo Document ID = 5d7ff03b-050f-4ace-8c7f-b793327163f8
Approver: 
Approval Date & Time: 05-Dec-2019 19:44:06 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 05-Dec-2019 20:26:49 GMT
Signature meaning: Approved
Approver:
Approval Date & Time: 06-Dec-2019 01:21:42 GMT
Signature meaning: Approved
PPD
PPD