A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Outpatient Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Baricitinib in Pediatric Patients With Moderate to Severe Atopic Dermatitis
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

Protocol I4V-MC-JAIP(c) 
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 
Outpatient Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Baricitinib in 
Pediatric Patients with Moderate-to-Severe Atopic Dermatitis 
NCT03952559 
Approval Date: 14-Feb-2023 

I4V-MC-JAIP(c) Clinical Protocol 
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LY3009104 
Protocol I4V-MC-JAIP(c) 
A Phase 3, Multicenter, Randomized, Double-blind, 
Placebo-controlled, Parallel-group, Outpatient Study 
Evaluating the Pharmacokinetics, Efficacy, and Safety of 
Baricitinib in Pediatric Patients with Moderate-to-Severe 
Atopic Dermatitis  
BREEZE-AD-PEDS 
EUDRA CTA 2018-000349-38 
Confidential Information 
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
baricitinib (LY3009104), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.   
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries. 
Baricitinib (LY3009104) 
Eli Lilly and Company 
Indianapolis, Indiana USA 46285 
Regulatory Agency Identifier Number(s) 
EU trial number:  2023-503898-38-00 
Approval Date: Protocol Amendment (c) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: VV-CLIN-074361 
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Protocol Amendment Summary of Changes Table  
 
DOCUMENT HISTORY 
Document 
Date 
Amendment (b) 
06-Aug-2020 
Amendment (a) 
12-Jun-2019 
Original Protocol 
06-Sep-2018 
Amendment [c]  
The amendment is considered to be substantial because it is likely to have a significant impact on 
the safety of the study participants 
Overall Rationale for the Amendment: 
The rationale of this amendment is to align with new EU Clinical Trial Regulation requirements 
and extend the study duration. 
Section # and Name 
Description of Change 
Brief Rationale 
1. Synopsis 
Included Regulatory Agency Identifier Number(s) 
For harmonization of the 
protocol 
Updated the section to align with the changes in the 
main body of the protocol 
For consistency 
2. Schedule of Activities 
4. Objectives and Endpoints 
5.1. Overall Design 
5.1.3. Period 3: Double-
blind Placebo-Controlled 
Treatment Period 
5.1.4. Period 4: Long-term 
Extension Treatment Period 
5.1.5. Period 5: 
Post-Treatment Follow-up 
10.3.3.3. 
Tertiary/Exploratory 
Analyses 
Extended Study Period 4 by up to an additional 
1 year for patients for whom a systemic JAK or 
biologic treatment is not available 
This extension of treatment will 
allow for continued efficacy 
and safety data collection and 
will allow patients to continue 
to receive baricitinib treatment 
for up to an additional 1 year 
until baricitinib is commercially 
available for the population or 
not approved.  
2. Schedule of Activities 
7.7.2. Use of Topical 
Corticosteroids 
Defined that sponsor will provide low- and 
moderate-potency TCS through study Visit 27. At 
Visit 28 and beyond, sponsor will not provide TCS. 
This will allow use of TCS 
products that are preferred by 
the patient and are locally 
available to the patient upon 
study completion. 
2. Schedule of Activities 
Defined that the collection of imaging (x-ray, MRI) 
is not required after the patient reaches 18 years of 
age  
Most patients will have 
completed growing by 18 years 
of age. Discontinuing the 
collection of imaging when 
growth is not expected will 
eliminate the risks associated 
with unnecessary x-ray 
exposure. 
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Section # and Name 
Description of Change 
Brief Rationale 
Revised footnote “a” and added footnote “s” 
To align with the additional 
visits 
4. Objectives and Endpoints 
10.3.3.3. 
Tertiary/Exploratory 
Analyses 
Added “Proportion of patients achieving 
SCORAD75 at 2, 3, 4, and 5 years during long-term 
extension.” as exploratory objective 
To align SCORAD analysis 
timepoints with IGA and EASI 
75 exploratory objectives  
9.4.3 Laboratory Tests 
Added a statement to refer Appendix 13 as 
incorporated Protocol Addendum (4) as a new 
Appendix 13 
To avoid country and region-
specific protocol versions in the 
EU 
Appendix 11. Additional 
Procedures for Countries 
Participating in the PK 
Lead-in Period (Study 
Period 2) 
Added this new appendix and included the content 
from PK Addendum (5). Also, updated the SoA as 
per current protocol amendment 
To avoid country and region-
specific protocol versions in the 
EU 
Appendix 12. EU-specific 
Requirements 
Added a new appendix applicable to EU only sites 
by including the content from Protocol Addenda 6, 7, 
8.4, and 12. Also, updated the SoA as per current 
protocol amendment. 
 12.1.
 12.2.
 12.3.
For harmonization of the 
protocol and to avoid country 
and region-specific protocol 
versions in the EU 
Appendix 13. Guidance for 
Blood Sampling When 
Volume Restrictions May 
apply 
Incorporated Protocol Addendum (4) as a new 
Appendix 13 to protocol and added a statement to 
refer this appendix in Section 9.4.3 
To avoid country and region-
specific protocol versions in the 
EU 
Revised Protocol Sections 
Removed this sections 
Updated according to internal 
Lilly guidance 
Throughout the protocol 
Minor formatting and editorial changes  
Minor, therefore, not detailed 
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Table of Contents  
Section 
Page  
Protocol I4V-MC-JAIP(c) A Phase 3, Multicenter, Randomized, 
Double-blind, Placebo-controlled, Parallel-group, Outpatient Study 
Evaluating the Pharmacokinetics, Efficacy, and Safety of Baricitinib 
in Pediatric Patients with Moderate-to-Severe Atopic Dermatitis ..........................................1 
Protocol Amendment Summary of Changes Table .......................................................................2 
Table of Contents .............................................................................................................................4 
1. 
Synopsis .................................................................................................................................11 
2. 
Schedule of Activities ............................................................................................................17 
3. 
Introduction ...........................................................................................................................38 
3.1. 
Study Rationale ................................................................................................................38 
3.2. 
Background.......................................................................................................................40 
3.3. 
Benefit/Risk Assessment ..................................................................................................42 
4. 
Objectives and Endpoints ......................................................................................................45 
5. 
Study Design .........................................................................................................................48 
5.1. 
Overall Design ..................................................................................................................48 
5.1.1. 
Period 1:  Screening .................................................................................................48 
5.1.2. 
Period 2:  Open-label PK lead-in .............................................................................49 
5.1.3. 
Period 3:  Double-blind Placebo-Controlled Treatment 
Period .......................................................................................................................51 
5.1.4. 
Period 4:  Long-term Extension Treatment Period ..................................................53 
5.1.5. 
Period 5:  Post-Treatment Follow-Up ......................................................................56 
5.2. 
Number of Participants .....................................................................................................56 
5.3. 
End of Study Definition....................................................................................................57 
5.4. 
Scientific Rationale for Study Design ..............................................................................57 
5.5. 
Justification for Dose ........................................................................................................58 
6. 
Study Population ...................................................................................................................60 
6.1. 
Inclusion Criteria ..............................................................................................................60 
6.2. 
Exclusion Criteria .............................................................................................................63 
6.3. 
Lifestyle Restrictions ........................................................................................................68 
6.4. 
Screen Failures .................................................................................................................68 
7. 
Treatments .............................................................................................................................69 
7.1. 
Treatments Administered .................................................................................................69 
7.1.1. 
Packaging and Labelling ..........................................................................................70 
7.1.2. 
Medical Devices .......................................................................................................70 
7.2. 
Method of Treatment Assignment ....................................................................................71 
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7.2.1. 
Selection and Timing of Doses ................................................................................71 
7.3. 
Blinding ............................................................................................................................71 
7.4. 
Dosage Modification ........................................................................................................72 
7.5. 
Preparation/Handling/Storage/Accountability .................................................................72 
7.6. 
Treatment Compliance .....................................................................................................73 
7.7. 
Concomitant Therapy .......................................................................................................73 
7.7.1. 
Permitted Medications and Procedures ....................................................................73 
7.7.2. 
Use of Topical Corticosteroids ................................................................................75 
7.7.3. 
Use of Antihistamines ..............................................................................................76 
7.7.4. 
Prohibited Medications and Procedures ...................................................................76 
7.7.5. 
Rescue Therapy ........................................................................................................77 
7.7.5.1. 
Rescue during Periods 2 and 3 ...........................................................................77 
7.7.5.2. 
Rescue during Period 4 ......................................................................................78 
7.8. 
Treatment after the End of the Study ...............................................................................79 
8. 
Discontinuation Criteria ........................................................................................................80 
8.1. 
Discontinuation from Study Treatment ............................................................................80 
8.1.1. 
Temporary Discontinuation from Study Treatment .................................................80 
8.1.2. 
Permanent Discontinuation from Study Treatment .................................................82 
8.1.3. 
Discontinuation of Inadvertently Enrolled Patients .................................................83 
8.2. 
Discontinuation from the Study ........................................................................................84 
8.3. 
Lost to Follow-Up ............................................................................................................84 
9. 
Study Assessments and Procedures .......................................................................................85 
9.1. 
Efficacy Assessments .......................................................................................................85 
9.1.1. 
Primary Efficacy Assessments .................................................................................85 
9.1.2. 
Secondary Efficacy Assessments .............................................................................85 
9.1.2.1. 
Eczema Area and Severity Index scores ............................................................85 
9.1.2.2. 
SCORing Atopic Dermatitis ...............................................................................85 
9.1.3. 
Immunological Measurements .................................................................................86 
9.1.4. 
Health Outcomes and Quality-of-Life Measures .....................................................86 
9.1.4.1. 
Patient-Oriented Eczema Measure .....................................................................86 
9.1.4.2. 
Itch Numeric Rating Scale .................................................................................86 
9.1.4.3. 
Skin Pain Numeric Rating Scale ........................................................................86 
9.1.4.4. 
Atopic Dermatitis Sleep Scale ............................................................................86 
9.1.4.5. 
Patient Global Impression of Severity ...............................................................87 
9.1.4.6. 
PROMIS Depression Short Form .......................................................................87 
9.1.4.7. 
PROMIS Anxiety Short Form ............................................................................87 
9.1.4.8. 
Infants’ Dermatitis Quality of Life Index...........................................................87 
9.1.4.9. 
Children’s Dermatology Life Quality Index ......................................................88 
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9.1.4.10. 
Dermatitis Family Impact Questionnaire ...........................................................88 
9.1.4.11. 
European Quality of Life–5 Dimensions–Youth ...............................................88 
9.1.4.12. 
Work Productivity and Activity Impairment 
Questionnaire:  Atopic Dermatitis - Caregiver ..................................................89 
9.1.4.13. 
Parent-Reported Itch Severity Measure .............................................................89 
9.1.4.14. 
Additional Assessments (TCS Use, Missed School Days) ................................89 
9.1.5. 
Product Acceptability and Palatability Assessments ...............................................89 
9.1.6. 
Appropriateness of Assessments ..............................................................................90 
9.2. 
Adverse Events .................................................................................................................90 
9.2.1. 
Serious Adverse Events ...........................................................................................91 
9.2.1.1. 
Suspected Unexpected Serious Adverse Reactions ...........................................92 
9.2.2. 
Adverse Events of Special Interest ..........................................................................92 
9.2.3. 
Complaint Handling .................................................................................................92 
9.3. 
Treatment of Overdose .....................................................................................................92 
9.4. 
Safety ................................................................................................................................93 
9.4.1. 
Electrocardiograms ..................................................................................................93 
9.4.2. 
Vital Signs ................................................................................................................93 
9.4.3. 
Laboratory Tests ......................................................................................................93 
9.4.4. 
Physical Exam ..........................................................................................................94 
9.4.4.1. 
Tanner Stage Scale .............................................................................................94 
9.4.5. 
Columbia Suicide Severity Rating Scale .................................................................94 
9.4.6. 
Self-Harm and Follow-Up Supplement Forms ........................................................95 
9.4.7. 
Tuberculosis Testing ................................................................................................95 
9.4.8. 
Hepatitis B Virus DNA Monitoring .........................................................................95 
9.4.9. 
Safety Monitoring ....................................................................................................95 
9.4.9.1. 
Hepatic Safety Monitoring .................................................................................96 
9.4.9.2. 
Venous Thromboembolic Event Assessment .....................................................97 
9.4.9.3. 
Growth Monitoring ............................................................................................97 
9.5. 
Pharmacokinetics ..............................................................................................................98 
9.5.1. 
Open-label PK Lead-in (Study Period 2) .................................................................98 
9.5.2. 
Double-blind Treatment Period (Study Period 3) ....................................................99 
9.6. 
Pharmacodynamics .........................................................................................................100 
9.6.1. 
Whole Blood Samples for Pharmacogenetic Research ..........................................100 
9.7. 
Biomarkers .....................................................................................................................100 
9.8. 
Medical Resource Utilization and Health Economics ....................................................101 
10. Statistical Considerations ....................................................................................................102 
10.1. Sample Size Determination ............................................................................................102 
10.2. Populations for Analyses ................................................................................................103 
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10.3. Statistical Analyses .........................................................................................................103 
10.3.1. 
General Statistical Considerations .........................................................................103 
10.3.2. 
Treatment Group Comparability ............................................................................105 
10.3.2.1. 
Patient Disposition ...........................................................................................105 
10.3.2.2. 
Patient Characteristics ......................................................................................105 
10.3.2.3. 
Concomitant Therapy .......................................................................................105 
10.3.2.4. 
Treatment Compliance .....................................................................................105 
10.3.3. 
Efficacy Analyses ..................................................................................................106 
10.3.3.1. 
Primary Analyses .............................................................................................106 
10.3.3.2. 
Secondary Analyses .........................................................................................106 
10.3.3.3. 
Tertiary/Exploratory Analyses .........................................................................108 
10.3.4. 
Safety Analyses ......................................................................................................108 
10.3.5. 
Pharmacokinetic/Pharmacodynamic Analyses ......................................................109 
10.3.6. 
Evaluation of Immunological Measures ................................................................110 
10.3.7. 
Other Analyses .......................................................................................................110 
10.3.7.1. 
Health Outcomes ..............................................................................................110 
10.3.7.2. 
Acceptability and Palatability ..........................................................................110 
10.3.7.3. 
Subgroup Analyses ...........................................................................................110 
10.3.8. 
Interim Analyses ....................................................................................................111 
10.3.8.1. 
Data Monitoring Committee ............................................................................112 
10.3.8.2. 
Adjudication Committee ..................................................................................113 
10.3.8.3. 
Unblinded Study Team for Regulatory Submission ........................................113 
11. References ...........................................................................................................................114 
12. Appendices ..........................................................................................................................122 
12.1. 
-Specific Requirements .........................................................................149 
12.2. 
-Specific Requirements........................................................................................154 
12.3. 
-Specific Requirements....................................................................................159 
 
 
 
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List of Tables 
Table 
Page 
Table JAIP.1. 
Schedule of Activities for Patients Participating in the Open-label PK 
Lead-in...............................................................................................................18 
Table JAIP.2. 
Schedule of Activities for Patients Randomized to Double-blind 
Treatment in Study Period 3 ..............................................................................28 
Table JAIP.3. 
Objectives and Endpoints ..................................................................................45 
Table JAIP.4. 
Treatment Regimens ..........................................................................................69 
Table JAIP.5. 
Criteria for Temporary Interruption of Investigational Product ........................81 
Table JAIP.6. 
Schedule of Activities for Patients Participating in the Open-label PK 
Lead-in.............................................................................................................148 
Table JAIP.7. 
Schedule of Activities for Patients Participating in the Open-label PK 
Lead-in.............................................................................................................152 
Table JAIP.8. 
Schedule of Activities for Patients Randomized to Double-blind 
Treatment in Study Period 3 ............................................................................153 
 
 
 
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List of Figures 
Figure 
Page 
Figure JAIP.1. 
Illustration of study design for Clinical Protocol I4V-MC-JAIP (PK 
Lead-in, Study Period 2). ..................................................................................51 
Figure JAIP.2. 
Illustration of study design for Clinical Protocol I4V-MC-JAIP 
(Double-Blinded Treatment, Study Period 3). ..................................................53 
Figure JAIP.3. 
Illustration of study design for Clinical Protocol I4V-MC-JAIP (Long-
term Extension, Study Period 4)........................................................................56 
 
 
 
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List of Appendices 
Appendix 
Page 
Appendix 1.
Abbreviations and Definitions .........................................................................123
Appendix 2.
Clinical Laboratory Tests ................................................................................128
Appendix 3.
Study Governance Considerations ..................................................................130
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality ..................135
Appendix 5.
Monitoring Tests for Confirmed VTE .............................................................136
Appendix 6.
Administration of Efficacy, Safety, Health Outcomes, and Quality of 
Life Measures ..................................................................................................137
Appendix 7.
Liver Function Testing and Hepatic Safety Monitoring .................................140
Appendix 8.
American Academy of Dermatology:  Criteria for the Diagnosis and 
Assessment of Atopic Dermatitis ....................................................................141
Appendix 9.
Classification of Potency for Topical Corticosteroids ....................................142
Appendix 10.
Provisions for Changes in Study Conduct During Exceptional 
Circumstances .................................................................................................143
Appendix 11.
Additional Procedures for Countries Participating in the PK Lead-in 
Period (Study Period 2) ...................................................................................147
Appendix 12.
EU-Specific Requirements ..............................................................................149
Appendix 13.
Guidance for Blood Sampling When Volume Restrictions May Apply .........165
Appendix 14.
Protocol Amendment History ..........................................................................166
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1. Synopsis  
Title of Study: 
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, 
Outpatient Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Baricitinib in 
Pediatric Patients with Moderate to Severe Atopic Dermatitis 
Regulatory Agency Identifier Number(s): 
EU trial number: 2023-503898-38-00 
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).  In addition to AD resulting from T cell 
activation, there is also evidence that a defective epidermal barrier contributes to the AD process.  
Patients with filaggrin mutations are at increased risk for developing AD, as filaggrin contributes 
to abnormal barrier function (Palmer et al. 2006).  Presentation is varied, but includes skin 
manifestations including pruritus, associated sleep disturbances, and subsequent skin infections.  
The course of disease includes relapses of varying duration and severity.  Atopic dermatitis is 
one of the most common chronic diseases in childhood.  The prevalence of AD is higher in 
children than in adults, and pediatric patients with AD are afflicted with a heavy disease burden.  
The prevalence of AD ranges from approximately 9% in teenagers to 14% in children 0 to 
4 years of age (Shaw et al. 2011).  In addition, the distribution of severity tends to shift to higher 
severities at older ages with older children being more likely to have moderate to severe disease 
(Silverberg and Simpson 2014).   
Atopic dermatitis has traditionally been treated with emollients and topical corticosteroids to 
address barrier dysfunction and immune abnormalities:  low-potency corticosteroids for mild 
cases, medium- and high-potency for moderate cases.  The standard of care remains medium- to 
high-potency topical corticosteroids in both adult and pediatric patients.  Although topical 
corticosteroids are used broadly in AD, patients with moderate to severe disease may not achieve 
good disease control with these treatments.  In addition, continuous long-term use of topical 
corticosteroids, particularly those with higher potency, is not recommended because of side 
effects.  Similar to adults, a need exists for new treatments that demonstrate safety and efficacy 
in pediatric patients who have responded inadequately to or who are intolerant to topical 
treatments. 
Baricitinib is an orally available, selective Janus kinase (JAK) inhibitor with potency and 
selectivity for JAK1 and JAK2 and less potency for JAK3 or tyrosine kinase 2 (TYK2) (Fridman 
et al. 2010).  The pathogenesis of AD is thought to be modulated through thymic stromal 
lymphopoietin (TSLP), interleukin (IL)-13, IL-4, IL-5, IL-22, and IL-31, many of which activate 
receptors with downstream signaling through intracellular JAK1/JAK2/TYK2 (Nomura and 
Kabashima 2016).  This activity profile suggests that baricitinib would inhibit cytokines involved 
in AD pathogenesis. 
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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 (RA) (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. 
2018); was effective in improving signs and symptoms of active systemic lupus erythematosus 
(Wallace et al. 2018); and in a recently completed Phase 2 study (I4V-MC-JAHG [JAHG]) was 
effective at reducing disease severity in adult patients with moderate-to-severe AD (Guttman-
Yassky et al. 2018).  In addition, baricitinib is being used to treat pediatric patients participating 
in an expanded access program (protocol I4V-MC-JAGA [JAGA]:  Compassionate Use Protocol 
for the Treatment of Autoinflammatory Syndromes) which has been ongoing since 2011 (Kim et 
al. 2018; Sanchez et al. 2018).  Safety information from the expanded access program has not 
identified any new safety signals for baricitinib beyond those identified in the Phase 3 studies in 
adult patients with RA. 
The mechanism of action, combined with demonstration of clinical benefit in inflammatory 
diseases involving joints, kidneys, and skin, and additional experience in pediatric patients with 
rare autoinflammatory diseases provides the rationale for evaluating baricitinib in pediatric 
patients with moderate-to-severe AD. 
Physicians with experience treating pediatric AD patients will participate as investigators in this 
clinical trial. 
Objective(s)/Endpoints: 
Objectives 
Endpoints 
Primary for Double-blind Treatment Period 
 
To demonstrate the superiority of each dose of 
baricitinib versus placebo in the treatment of 
patients with moderate-to-severe AD. 
 
 
Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at Week 16 
 
Primary for PK Lead-in Period 
 
To assess whether baricitinib exposure in 
pediatric patients receiving baricitinib high 
dose once daily is comparable to the exposure 
in adults receiving baricitinib 4-mg once 
daily. 
 
Comparability will be assessed using non-
compartmental methods (e.g., AUC and Cmax) 
Key Secondary 
These are prespecified objectives that will be adjusted 
for multiplicity  
 
 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week double-blind placebo-controlled 
treatment period as measured by improvement 
in signs and symptoms of AD. 
 
Proportion of patients achieving EASI75 at 
16 weeks 
 
Proportion of patients achieving EASI90 at 
16 weeks 
 
Mean change from baseline in EASI score at 
16 weeks 
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Objectives 
Endpoints 
 
Proportion of patients achieving SCORAD75 
at 16 weeks 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week double-blind placebo-controlled 
treatment period as assessed by 
patient-reported outcome measures.  
 
Proportions of patients achieving a 4-point 
improvement in Itch NRS at 1 week, 2 weeks, 
4 weeks, and 16 weeks for patients ≥10 years 
old 
Other Secondary 
These are prespecified objectives that will not be 
adjusted for multiplicity. 
 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week double-blind placebo-controlled 
period as measured by physician-assessed 
signs and symptoms of AD. 
 
Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at Week 4 
 
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 
 
Mean percent change from baseline in 
SCORAD at 16 weeks 
 
Proportion of patients achieving SCORAD90 
at 16 weeks 
 
Mean percent change from baseline in EASI 
score at 16 weeks 
 
Mean change from baseline in BSA affected 
at 16 weeks 
 
Proportion of patients developing skin 
infections requiring antibiotic treatment by 
Week 16 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week, double-blind, placebo-controlled 
treatment period as assessed by 
patient-reported outcome/QoL measures. 
 
Mean number of days without use of TCS 
over 16 weeks 
 
Mean gram quantity of TCS used over 16 
weeks (tube weights) 
 
Mean change from baseline in Itch NRS at 
1 week, 4 weeks and 16 weeks for patients 
≥10 years old 
 
Mean percent change from baseline in Itch 
NRS at 1 week, 4 weeks and 16 weeks for 
patients ≥10 years old 
 
Mean change in the PRISM at 1 week, 
2 weeks, 4 weeks, and 16 weeks for patients 
<10 years old 
 
Mean change from baseline in the total score 
of the POEM at 16 weeks 
 
Mean change in PGI-S-AD scores at 16 weeks 
 
Mean change from baseline in the PROMIS-
pediatric depression at 16 weeks  
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Objectives 
Endpoints 
 
Mean change from baseline in the PROMIS-
pediatric anxiety at 16 weeks 
 
Mean change from baseline in DFI at 16 
weeks 
 
Mean change in CDLQI/IDQOL scores at 16 
weeks 
 
Mean change in WPAI-AD-CG scores at 
16 weeks 
 
Mean change in EQ-5D-Y scores at 16 weeks. 
 
Mean change from baseline in the score of 
Item 2 of the ADSS at 1 week and 16 weeks 
for patients ≥10 years old. 
 
Mean change from baseline in Skin Pain NRS 
at 16 weeks for patients ≥10 years old 
 
To assess the patient acceptability and 
palatability of baricitinib tablets and oral 
suspension.  
 
Assessment of tablet or oral suspension 
product acceptability and palatability during 
the Open-label PK Lead-in period 
 
To characterize the pharmacokinetic profile of 
the baricitinib in pediatric patients with AD. 
 
Population PK Analysis based on sparse 
sampling over 16 weeks (Study Period 3) with 
secondary endpoints including Cmax, AUC, 
and t1/2  
 
To evaluate the potential effects of baricitinib 
on the cellular and humoral immune system. 
 
Change of IgG titers from pre-vaccination to 
4 weeks and 12 weeks post vaccination in 
patients eligible for vaccination with tetanus, 
diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to 
local guidelines 
 
To assess efficacy of baricitinib during 
longer-term treatment. 
 
Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at 1 year. 
 
Proportion of patients achieving EASI75 at 1 
year. 
 
Proportion of patients achieving SCORAD75 
at 1 year  
 
To assess growth and bone safety of 
baricitinib during longer-term treatment. 
 
Mean changes in growth (height and weight), 
growth velocity, and bone age over the course of 
treatment during the long-term extension treatment 
period 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 15 
LY3009104 
Abbreviations:  AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; AUC = area under the 
concentration curve; BSA = body surface area; CDLQI = Children’s Dermatology Life Quality Index; 
Cmax = maximum concentration; DFI = Dermatology Family Impact; EASI = Eczema Area and Severity Index; 
EQ-5D-Y = the European Quality of Life–5 Dimensions–Youth; IDQOL = Infant’s Dermatitis Quality of Life 
Index; IgG = immunoglobulin G; IGA = Investigator’s Global Assessment; NRS = numeric rating scale; 
PK = pharmacokinetic; QoL = quality of life; PGI-S-AD = Patient Global Impression of Severity–Atopic 
Dermatitis; POEM = Patient-Oriented Eczema Measure; PRISM = Parent-Reported Itch Severity Measure; 
PROMIS = Patient-Reported Outcomes Measurement Information System; t1/2 = half-life; TCS = topical 
corticosteroids; SCORAD = SCORing Atopic Dermatitis; WPAI-AD-CG = Work Productivity and Activity 
Impairment:  Atopic Dermatitis – Caregiver 
 
Summary of Study Design:   
Study I4V-MC-JAIP (JAIP) is a multicenter, randomized, double-blind, placebo-controlled, 
parallel-group, outpatient study evaluating the pharmacokinetics, efficacy, and safety of 
baricitinib in pediatric patients with moderate-to-severe AD who have responded inadequately to 
or who are intolerant to topical treatments. 
Treatment Arms and Duration:   
The study is divided into 5 periods, a 5-week Screening period, a 2-week Open-label 
pharmacokinetic (PK) Lead-in period, a 16-week Double-Blind Treatment period, an up to 
5-year Long-term Extension period, and a 4-week Post-treatment Follow-up period.  
The Open-label PK Lead-in period will evaluate if exposure to baricitinib high dose in pediatric 
patients is comparable with baricitinib exposure in adults.  Patients will receive oral baricitinib at 
a fixed high dose by age group once daily (QD) for approximately 2 weeks.  Enrollment will be 
staggered by age group (10 to <18 years, 6 to <10 years, and 2 to <6 years), with older groups 
enrolling before younger groups.  Enrollment of an age group into the Double-blind Treatment 
period will begin only after analysis of the PK data for that age group from the PK lead-in has 
been completed. 
Number of Patients:  
Approximately 465 will be enrolled into this study.  
Approximately 25 patients will be enrolled into the PK lead-in (at least 15 patients aged 10 to 
<18 years old and at least 10 patients aged 2 to <10 years old). 
Approximately 440 patients will be enrolled into the Double-blind Treatment period (with at 
least 320 patients aged 10 to <18 years old and at least 120 patients aged 2 to <10 years old.   
Statistical Analysis: 
Approximately 25 patients will be enrolled into the Open-label PK Lead-in (Study Period 2) and 
may continue on open-label treatment during the long-term extension (Study Period 4).  Data 
from patients participating in the PK lead-in will be analyzed separately from patients 
randomized into the Double-blind Treatment (Study Period 3).   
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
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LY3009104 
Approximately 440 patients 2 to <18 years of age will participate in the Double-blind Treatment 
period (Study Period 3) and will be randomized at a 1:1:1:1 ratio to receive placebo QD, 
baricitinib low dose QD, baricitinib medium dose QD, or baricitinib high dose QD (110 patients 
in each treatment group).  Patients will be stratified at randomization according to disease 
severity (Investigator’s Global Assessment [IGA] 3 vs. 4) and geographic region if the planned 
country allocation justifies. 
The study will be carried out using an intent-to-treat population defined as all randomized 
patients for the efficacy analyses.  The primary efficacy measure is the binary outcome of 
response defined as an IGA score of 0 or 1 (clear or almost clear) with a ≥2-point improvement 
at Week 16.  Given the sample size and a non-responder imputation (NRI) method for missing 
data, the current sample size (N=440 with 1:1:1:1 randomization) will ensure a >95% power to 
detect any difference between the baricitinib high dose and placebo treatment groups or the 
baricitinib medium dose and placebo treatment groups, each using a 2-sided alpha of 0.05, 
assuming a 10% placebo, 25% medium dose, and 30% high dose response rate for the primary 
endpoint.  Patients who are rescued or discontinue treatment will be considered non-responders.  
Treatment group comparisons for binary efficacy response measures will be analyzed using a 
logistic regression.  The primary analysis will be conducted using a logistic regression analysis 
with region, disease severity (IGA), age, treatment group, and treatment group-by-age interaction 
in the model.  Other secondary measures of efficacy that are continuous will be analyzed using 
mixed-model repeated measures (MMRM) methodology.  Placebo multiple imputation and last 
observation carried forward methods will also be used for analysis of continuous endpoints.  
Population PK and PK/PD analyses based on data from the Double-blind Treatment period will 
be used to characterize the PK of baricitinib and to explore relationships between baricitinib 
exposure and efficacy and/or safety endpoints.  In the case of slower enrollment for the younger 
pediatric subgroup (i.e., the older pediatric subgroup completes the double-blind treatment period 
more than 6 months earlier than the anticipated completion date for the younger subgroup of 
pediatric patients), the older pediatric subgroup may be analyzed first according to a pre-planned 
analytical approach to support timely regulatory submission.  
Safety analyses will be conducted using the safety population defined as all randomized patients 
who received at least 1 dose of investigational product (IP) and who did not discontinue from the 
study for the reason ‘Lost to Follow-up’ at the first postbaseline visit.   
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 17 
LY3009104 
2. Schedule of Activities  
 
The Schedule of Activities described below should be followed for all participants enrolled in 
Study JAIP.  In the event participation in this study is affected by exceptional circumstances 
(such as pandemics or natural disasters), please refer to Appendix 10 and consult with the 
sponsor’s representative for additional guidance.
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 18 
LY3009104 
Table JAIP.1. 
Schedule of Activities for Patients Participating in the Open-label PK Lead-in  
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
 
Period 1 
Period 2 
Period 4 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
100 
112 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria review 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed 
consent/Assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical assessments 
and general study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Substance Use 
(alcohol, tobacco use 
for patients ≥10 years) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and current 
AD treatments 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heightb 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP and 
Pulse)b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Occipital frontal 
circumference 
measurement in 
patients <3 years old 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 19 
LY3009104 
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
 
Period 1 
Period 2 
Period 4 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
100 
112 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tanner Staging in 
patients ≥8 years old 
(see Section 9.4.4.1.) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom-directed 
physical examc 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (single) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB testd  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Read PPD if applicable 
(48–72 hours post PPD)e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-existing Conditions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medication 
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 
 
 
 
 
 
 
 
 
 
ePRO (patient diary) 
returned 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Begin treatment with 
open-label baricitinib 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP tablets dispensed 
(patients ≥10 years old) 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP suspension 
dispensed (patients <10 
years old) 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 20 
LY3009104 
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
 
Period 1 
Period 2 
Period 4 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
100 
112 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP returned and 
compliance assessed  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense and weigh 
(tube with cap) TCSf  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weigh (tube with cap) 
and record returned 
TCSf 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
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 
SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Health Outcomes 
Measures and Other 
Questionnaires  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
POEMg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDLQI /IDQOLg 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DFIg 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS-Depressiong 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS-Anxietyg 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D-Yg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
WPAI-AD-CGg 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Missed School Days 
for school age 
childreng  
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
PRISMg 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Itch NRSg  
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 21 
LY3009104 
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
 
Period 1 
Period 2 
Period 4 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
100 
112 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Skin Pain NRSg 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
ADSSg 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
PGI-S-ADg 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
TCS Useg 
 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Palatability and 
Acceptability 
 
X 
 
Xg 
 
 
 
 
 
 
 
 
 
 
 
C-SSRS and Self-Harm 
Supplementh  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Self-Harm Follow-up 
Formi 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical chemistryj, q 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyq 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipids (fasting)k, q 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
IGF-1 and IGFBP-3q 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
Left hand x-rayl (see 
Section 9.4.9.3 for 
ongoing patients) 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X-ray of the kneel 
(see Section 9.4.9.3 for 
ongoing patients) 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Gonadal hormones 
(patients 8 to <18 years 
old)m, q 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
Serum Pregnancyn 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 22 
LY3009104 
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
 
Period 1 
Period 2 
Period 4 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
100 
112 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TSH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HCV antibodyo 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBV testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBV DNAp 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisq 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Pregnancyn, q 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacogenetics:  
bloodq 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum IgEq 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory storage 
samples (serum and 
plasma)q 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RNA and biomarkers:  
bloodq 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Baricitinib plasma 
concentration (PK 
sample)r 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Antipneumococcal IgG 
multianalyte Ab assay* 
 
 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination based on 
the vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to local recommended schedule of vaccination, IgG titers 
for eligible vaccine will be evaluated at prevaccination, 4 weeks post vaccination, and 12 weeks post 
vaccination. 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 23 
LY3009104 
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
 
Period 1 
Period 2 
Period 4 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
100 
112 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-tetanus toxoid IgG, 
anti-diphtheria toxoid, 
and anti-pertussis toxoid 
Ab assay* 
 
 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination based on 
the vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to local recommended schedule of vaccination, IgG titers 
for eligible vaccine will be evaluated at prevaccination, 4 weeks post vaccination, and 12 weeks post 
vaccination. 
 
 
Long-term Extension Treatment 
PTF/U 
 
Period 4 – Extended (PK Lead-in Patients) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from initiation of baricitinib treatment  
124 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ± 4 
after last 
dose 
Clinical assessments and general study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heightb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs (BP and Pulse)b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Occipital frontal circumference measurement in 
patients <3 years old 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Symptom-directed physical examc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 24 
LY3009104 
 
Long-term Extension Treatment 
PTF/U 
 
Period 4 – Extended (PK Lead-in Patients) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from initiation of baricitinib treatment  
124 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ± 4 
after last 
dose 
Clinical assessments and general study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP tablets dispensed (patients ≥10 years old) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
IP suspension dispensed (patients <10 years old) 
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 
 
Dispense and weigh (tube with cap) TCSf  
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Weigh (tube with cap) and record returned TCSf   
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
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 
SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Health Outcomes Measures and Other 
Questionnaires  
 
 
 
 
 
 
 
 
 
 
 
 
 
POEMg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
CDLQI /IDQOLg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
DFIg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
PROMIS-Depressiong 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
PROMIS-Anxietyg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
EQ-5D-Yg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
WPAI-AD-CGg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
C-SSRS and Self-Harm Supplementh  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Self-Harm Follow-up Formi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 25 
LY3009104 
 
Long-term Extension Treatment 
PTF/U 
 
Period 4 – Extended (PK Lead-in Patients) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from initiation of baricitinib treatment  
124 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ± 4 
after last 
dose 
Clinical assessments and general study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical chemistryj 
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 
Lipids (fasting)k 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
IGF-1 and IGFBP-3 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
Left hand x-rayl (see Section 9.4.9.3 for ongoing 
patients) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X-ray of the kneel 
(see Section 9.4.9.3 for ongoing patients) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Gonadal hormones (patients 8 to <18 years old)m 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
HBV DNAp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X  
X 
Urine Pregnancyn 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum IgE 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Antipneumococcal IgG multianalyte Ab assay* 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination 
based on the vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to local recommended schedule of vaccination, 
IgG titers for eligible vaccine will be evaluated at prevaccination, 4 weeks post vaccination, 
and 12 weeks post vaccination. 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
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LY3009104 
 
Long-term Extension Treatment 
PTF/U 
 
Period 4 – Extended (PK Lead-in Patients) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from initiation of baricitinib treatment  
124 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ± 4 
after last 
dose 
Clinical assessments and general study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-tetanus toxoid IgG, anti-diphtheria toxoid, and 
anti-pertussis toxoid Ab assay* 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination 
based on the vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to local recommended schedule of vaccination, 
IgG titers for eligible vaccine will be evaluated at prevaccination, 4 weeks post vaccination, 
and 12 weeks post vaccination. 
 
Abbreviations:  Ab = antibody; AD = Atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BP = blood pressure; C-SSRS = Columbia Suicide Severity 
Rating Scale 11 categories suicidal ideation/suicidal behavior; CDLQI = Children’s Dermatology Life Quality Index; DFI = Dermatitis Family Impact; 
EASI = Eczema Area and Severity Index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EQ-5D-Y = The European Quality of 
Life-5 Dimensions Youth; ET = early termination; ePRO = electronic patient reported outcomes (device); HBcAb = hepatitis B core antibody; 
HBV = hepatitis B virus; HCV = hepatitis C virus; IDQOL = Infant’s Dermatitis Quality of Life Index; IgE = Immunoglobulin E; IGFBP-3 = insulin-like 
growth factor binding protein-3; IgG = Immunoglobulin G; IP = investigational product; IWRS = interactive web-response system; NRS = numeric rating 
scale; PGI-S-AD = Patient Global Impression of Severity – Atopic Dermatitis; PK = pharmacokinetics; POEM = Patient Oriented Eczema Measure; 
PPD = purified protein derivative; PRISM = Parent-Reported Itch Severity Measure; PROMIS = Patient-Reported Outcomes Measurement Information 
System; PTF/U = post-treatment follow-up; SCORAD = SCORing Atopic Dermatitis; TB = tuberculosis; TCS = topical corticosteroids; TSH = thyroid 
stimulating hormone; vIGA-AD = validated investigator’s global assessment for atopic dermatitis; WPAI-AD-CG = Work Productivity and Activity 
Impairment-Atopic Dermatitis-Caregiver. 
a An early termination visit should be conducted if a patient discontinues from the study before Visit 31.  Visit 801 is the post-treatment follow-up visit, which 
occurs after the patient has been off IP for approximately 4 weeks.  Patients who have permanently discontinued IP but remain in the study for more than 
28 days without IP will only complete Visit 31/ET; Visit 801 (follow-up visit) is not required. Patient health outcomes assessments (POEM, CDLQI/IDQOL, 
DFI, PROMIS-Depression, PROMIS-Anxiety, EQ-5D-Y, WPAI-AD-CG) are collected for the early termination visit but are not collected at Visit 31. 
b Height will be measured using a stadiometer and Sponsor-provided instructions.  Blood pressure readings will be collected using the appropriate size pediatric 
blood pressure cuffs. 
c The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints. 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
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LY3009104 
d TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®.  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.  
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 
Only required for patients who have been prescribed sponsor-provided TCS. At Visit 28 and beyond, TCS will no longer be provided by the sponsor.  
g The following measures (POEM, CDLQI/IDQOL, DFI, PROMIS-Depression and Anxiety, EQ-5D-Y, WPAI-AD-CG, and palatability/acceptability as noted) 
should be completed prior to any clinical assessments being performed on days when study visits occur.  The following measures are collected via daily diary 
and should be completed at the end of the patient’s day:  PGI-S-AD, Itch NRS, Skin Pain NRS, ADSS, PRISM, missed school days and TCS use. 
h Suicidal ideation and behavior subscales excerpt – Adapted for the assessment of 11 preferred ideation and behavior categories.  The C-SSRS will only be 
collected in patients ≥7 years old. 
i 
The Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form. 
j 
Clinical chemistry will include estimated glomerular filtration rate (eGFR, calculated using Bedside Schwartz 2009 formula) calculated by the central 
laboratory from serum creatinine.  
k Fasting lipid profile:  Patients should not eat or drink anything except water for 4 to 12 hours (depending on age and weight as specified in Section 9.4.3) prior 
to sample collection.  If a patient attends these visits in a nonfasting state, this will not be considered to be a protocol violation. 
l 
Left hand and knee x-rays at an early termination visit is not required if previously taken within 6 months of the early termination visit. The collection of x-
rays and other imaging procedures should be discontinued after the patient reaches 18 years of age. 
m Estradiol (for females) or testosterone (for males) will be collected for the assessment of maturation in patients aged 8 to <18 years. 
n Pregnancy tests prior to first dose of investigational product for females ≥10 years old of age (<10 years at investigator discretion) if menarche reached or if 
there is reason to believe the patient is sexually active.  Pregnancy test results from Visit 2 must be known prior to first dose of investigational product.  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. 
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 (see Section 9.4.8). 
q At Visit 2 all laboratory samples, with the exception of PK samples, will be obtained prior to the first dose of IP. 
r PK samples will be collected as described in Section 9.5. 
s At Visit 27, patients should be discontinued from study treatment and begin study discontinuation procedures unless sponsor’s written approval is obtained to 
allow the patient to continue on study treatment.  Refer to Section 5.1.4.   
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 28 
LY3009104 
Table JAIP.2. 
Schedule of Activities for Patients Randomized to Double-blind Treatment in Study Period 3  
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria 
review 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed 
consent/Assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical assessments 
and general study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Substance Use 
(alcohol, tobacco use 
for patients ≥10 years 
old) 
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 
Heightb 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP and 
Pulse)b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Occipital frontal 
circumference 
measurement in 
patients <3 years old 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 29 
LY3009104 
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Tanner Staging in 
patients ≥8 years old 
(see Section 9.4.4.1.) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom-directed 
physical examc 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (single) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB testd  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Read PPD if applicable 
(48–72 hours post 
PPD)e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-existing 
Conditions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medication 
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 
 
 
 
 
 
 
 
 
 
 
 
 
ePRO (patient diary) 
returned 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP tablets dispensed 
(patients ≥10 years old) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP suspension 
dispensed (patients <10 
years old) 
 
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 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 30 
LY3009104 
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Dispense and weigh 
(tube with cap) TCSf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weigh (tube with cap) 
and record returned 
TCSf   
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
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 
SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Health Outcomes 
Measures and Other 
Questionnaires 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
POEMg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDLQI /IDQOLg 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
DFIg 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS-Depressiong 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
PROMIS-Anxietyg 
X 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D-Yg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
WPAI-AD-CGg 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Missed School Days 
for school age 
childreng  
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
PRISMg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Itch NRSg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Skin Pain NRSg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
ADSSg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
PGI-S-ADg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
TCS Useg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 31 
LY3009104 
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
C-SSRS and Self-
Harm Supplementh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Self-Harm Follow-up 
Formi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical chemistryj, q 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyq 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipids (fasting)k, q 
 
X 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
IGF-1 and IGFBP-3q 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
Left hand x-rayl (see 
Section 9.4.9.3 for 
ongoing patients) 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
X-ray of the kneel (see 
Section 9.4.9.3 for 
ongoing patients) 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Gonadal hormones 
(patients 8 to <18 years 
old)m, q 
 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
Serum Pregnancyn 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TSH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HCV antibodyo 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBV testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HBV DNAp 
X 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisq 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine Pregnancyn, q 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 32 
LY3009104 
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Pharmacogenetics:  
bloodq 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum IgEq 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory storage 
samples (serum and 
plasma)q 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RNA and biomarkers:  
bloodq 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Baricitinib plasma 
concentration (PK 
sample)r 
 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Antipneumococcal IgG 
multianalyte Ab assay* 
 
 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination 
based on the vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to local recommended schedule of vaccination, IgG 
titers for eligible vaccine will be evaluated at prevaccination, 4 weeks post vaccination, and 
12 weeks post vaccination. 
Anti-tetanus toxoid IgG, 
anti-diphtheria toxoid, 
and anti-pertussis toxoid 
Ab assay* 
 
 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination 
based on the vaccination schedule of each patient 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to local recommended schedule of vaccination, IgG 
titers for eligible vaccine will be evaluated at prevaccination, 4 weeks post vaccination, and 
12 weeks post vaccination. 
 
 
Approved on 14 Feb 2023 GMT

I4V-MC-JAIP(c) Clinical Protocol 
Page 33 
LY3009104 
 
Long-term Extension Treatment  
PTF/U 
 
Period 4 – Extended  
(Patients Randomized to Double-Blind Treatment at Visit 2) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from randomization 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
268 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 
after 
last 
dose 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Heightb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs (BP and Pulse)b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Occipital frontal circumference 
measurement in patients <3 
years old 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Symptom-directed physical 
examc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP tablets dispensed (patients 
≥10 years old) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
IP suspension dispensed 
(patients <10 years old) 
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 
 
Dispense and weigh (tube with 
cap) TCSf 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Weigh (tube with cap) and 
record returned TCSf   
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Scales 
 
 
 
 
 
 
 
 
 
 
 
 
 
vIGA-AD 
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 
SCORAD 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Long-term Extension Treatment  
PTF/U 
 
Period 4 – Extended  
(Patients Randomized to Double-Blind Treatment at Visit 2) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from randomization 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
268 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 
after 
last 
dose 
Health Outcomes Measures and 
Other Questionnaires 
 
 
 
 
 
 
 
 
 
 
 
 
 
POEMg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
CDLQI /IDQOLg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
DFIg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
PROMIS-Depressiong 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
PROMIS-Anxietyg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
EQ-5D-Yg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
WPAI-AD-CGg 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
C-SSRS and Self-Harm 
Supplementh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Self-Harm Follow-up Formi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical chemistryj 
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 
Lipids (fasting)k 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
IGF-1 and IGFBP-3 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
Left hand x-rayl (see Section 
9.4.9.3 for ongoing patients) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X-ray of the kneel (see Section 
9.4.9.3 for ongoing patients) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Gonadal hormones (patients 8 
to <18 years old)m 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
HBV DNAp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X  
X 
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Long-term Extension Treatment  
PTF/U 
 
Period 4 – Extended  
(Patients Randomized to Double-Blind Treatment at Visit 2) 
Period 
5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s 
28s 
29s 
30s 
31s/ 
ETa 
801 
Weeks from randomization 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
268 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 
after 
last 
dose 
Urine Pregnancyn 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum IgE 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
Baricitinib plasma 
concentration (PK sample)r 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Antipneumococcal IgG 
multianalyte Ab assay* 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination based on the 
vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or pneumococcal 
conjugate vaccine according to local recommended schedule of vaccination, IgG titers for eligible vaccine will 
be evaluated at prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination. 
 
Anti-tetanus toxoid IgG, anti-
diphtheria toxoid, and anti-
pertussis toxoid Ab assay* 
At relevant visits for prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination based on the 
vaccination schedule of each patient. 
  *If patients are eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) and/or pneumococcal 
conjugate vaccine according to local recommended schedule of vaccination, IgG titers for eligible vaccine will 
be evaluated at prevaccination, 4 weeks post vaccination, and 12 weeks post vaccination. 
 
Abbreviations:  Ab = antibody; AD = Atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; BP = blood pressure; C-SSRS = Columbia Suicide Severity 
Rating Scale 11 categories suicidal ideation/suicidal behavior; CDLQI = Children’s Dermatology Life Quality Index; DFI = Dermatitis Family Impact; 
EASI = Eczema Area and Severity Index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EQ-5D-Y = The European Quality of 
Life-5 Dimensions Youth; ET = early termination; ePRO = electronic patient reported outcomes (device); HBcAb = hepatitis B core antibody; 
HBV = hepatitis B virus; HCV = hepatitis C virus; IDQOL = Infant’s Dermatitis Quality of Life Index; IgE = immunoglobulin E; IGFBP-3 = insulin-like 
growth factor binding protein-3; IgG = immunoglobulin G; IP = investigational product; IWRS = interactive web-response system; NRS = numeric rating 
scale; PGI-S-AD = Patient Global Impression of Severity – Atopic Dermatitis; PK = pharmacokinetics; POEM = Patient Oriented Eczema Measure; 
PPD = purified protein derivative; PRISM = Parent-Reported Itch Severity Measure; PROMIS = Patient-Reported Outcomes Measurement Information 
System; PTF/U = post-treatment follow-up; SCORAD = SCORing Atopic Dermatitis; TB = tuberculosis; TCS = topical corticosteroids; TSH = thyroid 
stimulating hormone; vIGA-AD = validated investigator’s global assessment for atopic dermatitis; WPAI-AD-CG = Work Productivity and Activity 
Impairment-Atopic Dermatitis-Caregiver. 
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a An early termination visit should be conducted if patient discontinues from the study before Visit 31.  Visit 801 is the post-treatment follow-up visit, which 
occurs after the patient has been off IP for approximately 4 weeks.  Patients who have permanently discontinued IP but remain in the study for more than 28 
days without IP will only complete Visit 31/ET; Visit 801 (follow-up visit) is not required. Patient health outcomes assessments (POEM, CDLQI/IDQOL, 
DFI, PROMIS-Depression, PROMIS-Anxiety, EQ-5D-Y, WPAI-AD-CG) are collected for the early termination visit but are not collected at Visit 31. 
b Height will be measured using a stadiometer and Sponsor-provided instructions.  Blood pressure readings will be collected using the appropriate size pediatric 
blood pressure cuffs. 
c The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints. 
d TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®.  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. 
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 For patients prescribed sponsor-provided TCS as background treatment. At Visit 28 and beyond, TCS will no longer be provided by the sponsor. 
g The following measures (POEM, CDLQI/IDQOL, DFI, PROMIS-Depression and Anxiety, EQ-5D-Y, and WPAI-AD-CG) should be completed prior to any 
clinical assessments being performed on days when study visits occur.  The following measures are collected via daily diary and should be completed at the 
end of the patient’s day:  PGI-S-AD, Itch NRS, Skin Pain NRS, ADSS, PRISM, missed school days, and TCS use. 
h Suicidal ideation and behavior subscales excerpt – Adapted for the assessment of 11 preferred ideation and behavior categories.  The C-SSRS will only be 
collected in patients ≥7 years old. 
i 
The Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form. 
j 
Clinical chemistry will include estimated glomerular filtration rate (eGFR, calculated using Bedside Schwartz 2009 formula) calculated by the central 
laboratory from serum creatinine.  
k Fasting lipid profile:  Patients should not eat or drink anything except water for 4 to 12 hours (depending on age and weight as specified in Section 9.4.3) prior 
to sample collection.  If a patient attends these visits in a nonfasting state, this will not be considered to be a protocol violation. 
l 
Left hand and knee x-rays at an early termination visit is not required if previously taken within 6 months of the early termination visit. The collection of x-
rays and other imaging procedures should be discontinued after the patient reaches 18 years of age. 
m Estradiol (for females) or testosterone (for males) will be collected for the assessment of maturation in patients aged 8 to <18 years. 
n Pregnancy tests prior to first dose of investigational product for females ≥10 years old of age (<10 years at investigator discretion) if menarche reached or if 
there is reason to believe the patient is sexually active.  Pregnancy test results from Visit 2 must be known prior to first dose of investigational product.  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. 
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 (see Section 9.4.8). 
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q At Visit 2 all laboratory samples, with the exception of PK samples, will be obtained prior to the first dose of IP. 
r 
 PK samples will be collected as described in Section 9.5.  
s At Visit 27, patients should be discontinued from study treatment and begin study discontinuation procedures unless sponsor’s written approval is obtained to 
allow the patient to continue on study treatment.  Refer to Section 5.1.4.   
 
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3. Introduction  
3.1. Study 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).  In addition to AD resulting from T cell 
activation, there is also evidence that a defective epidermal barrier contributes to the AD process.  
Patients with filaggrin mutations are at increased risk for developing AD, as filaggrin contributes 
to abnormal barrier function (Palmer et al. 2006).  Presentation is varied, but includes skin 
manifestations, including pruritus, associated sleep disturbances, and subsequent skin infections.  
The course of disease includes relapses of varying duration and severity.  Atopic dermatitis is 
one of the most common chronic diseases in childhood.  The prevalence of AD is higher in 
children than in adults, and pediatric patients with AD are afflicted with a heavy disease burden.  
The prevalence of AD ranges from approximately 9% in teenagers to 14% in children 0 to 
4 years of age (Shaw et al. 2011).  In addition, the distribution of severity tends to shift to higher 
severities at older ages with older children being more likely to have moderate to severe disease 
(Silverberg and Simpson 2014).   
Atopic dermatitis has traditionally been treated with emollients and topical corticosteroids (TCS) 
to address barrier dysfunction and immune abnormalities:  low-potency TCS for mild cases, 
medium- and high-potency TCS for moderate cases.  The standard of care remains medium to 
high-potency TCS in both adult and pediatric patients.  Although TCS are used broadly in AD, 
patients with moderate to severe disease may not achieve good disease control with these 
treatments.  In a recently published study of dupilumab with concomitant TCS in adult patients 
with moderate-to-severe AD (Blauvelt et al. 2017), only 12% of patients randomized to placebo 
with TCS achieved clear or almost clear skin after 16 weeks of treatment.  It is generally 
accepted that TCS response and intolerance in pediatric patients is similar to adults (Lan et al. 
2003; Tan and Langley 2004; Lubbe et al. 2006); however, given their larger body surface area 
to weight ratio, children are at greater risk for systemic effects from TCS use (Eichenfield et al. 
2014a).  Topical calcineurin inhibitors are approved for the treatment of AD in pediatric patients 
from the age of 2 with inadequate response or intolerance to TCS (tacrolimus) or where 
treatment with TCS is either inadvisable or not possible (pimecrolimus).  In a recent meta-
analysis of clinical trial data of almost 7,000 patients treated over the last 15 years, either with 
TCS or topical calcineurin inhibitors (TCNIs), efficacy was considered similar between the 
2 drug categories (Broeders et al. 2016).  Although treatment guidelines have recommended the 
use of TCNIs in the pediatric population, this recommendation is limited to use based on 
individual clinical assessment in specific clinical situations (NICE 2007; Eichenfield et al. 
2014a; Werfel et al. 2016b).  Ciclosporin is the only approved systemic treatment for AD (only 
approved in some countries) for pediatric patients and is restricted to the treatment of patients 
≥16 years old with severe AD when systemic therapy is required.  Ciclosporin may be associated 
with toxicity and side effects, and use is time-limited due to end-organ toxicity, including 
hypertension and renal toxicity.  While no specific data on off-label use in younger children are 
available, use is considered very rare given that this treatment regimen is already rarely used in 
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AD adults (Schmitt et al. 2009).  Similar to adults, a need exists for new treatments that 
demonstrate safety and efficacy in pediatric patients who have responded inadequately to or who 
are intolerant to topical treatments. 
Baricitinib is an orally available, selective Janus kinase (JAK) inhibitor with potency and 
selectivity for JAK1 and JAK2 and less potency for JAK3 or tyrosine kinase 2 (TYK2) (Fridman 
et al. 2010).  The pathogenesis of AD is thought to be modulated through thymic stromal 
lymphopoietin (TSLP), interleukin (IL)-13, IL-4, IL-5, IL-22, and IL-31, many of which activate 
receptors with downstream signaling through intracellular JAK1/JAK2/TYK2 (Nomura and 
Kabashima 2016).  This activity profile suggests that baricitinib would inhibit cytokines involved 
in AD pathogenesis.  The JAK-STAT signaling pathway is functional from infancy, and 
aberrations in JAK-STAT signaling are implicated in other rare autoinflammatory diseases with 
onset within the first year of life (Liu et al. 2012; Liu et al. 2014), supporting the assumption that 
a JAK inhibitor such as baricitinib will be efficacious in the treatment of AD in both adult and 
pediatric patients. 
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 (RA) (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. 
2018); was effective in improving signs and symptoms of active systemic lupus erythematosus 
(Wallace et al. 2018); and in a recently completed Phase 2 study (I4V-MC-JAHG [JAHG]) was 
effective at reducing disease severity in adult patients with moderate-to-severe AD (Guttman-
Yassky et al. 2018).  In addition, baricitinib is being used to treat pediatric patients participating 
in an expanded access program (protocol I4V-MC-JAGA [JAGA]:  Compassionate Use Protocol 
for the Treatment of Autoinflammatory Syndromes) which has been ongoing since 2011 (Kim et 
al. 2018; Sanchez et al. 2018).  More than 30 patients ages 2 months to <18 years have been 
enrolled in the program as of June 2018.  Safety information from the expanded access program 
has not identified any new safety signals for baricitinib beyond those identified in the Phase 3 
studies in adult patients with RA. 
The current study will investigate a range of baricitinib doses that produce comparable exposures 
between pediatric patients and adults.  The assumption that similar exposures of baricitinib in 
adults and pediatric patients will result in similar response relies on the similarities in AD disease 
manifestation, aetiology, pathophysiology, response to existing therapies, and the similarity in 
the target populations to be enrolled in the adult and pediatric baricitinib studies.  This 
assumption has recently been supported by a consensus committee formed in partnership with 
the Pediatric Dermatology Research Alliance (PeDRA, a predominantly North American 
network with some European involvement); the US National Eczema Association (NEA), and 
the International Eczema Council (IEC 2017) (Siegfried et al. 2018).  
Given the prevalence of AD and the need for new AD treatments with demonstrated efficacy and 
safety in the pediatric population, the mechanism of action, combined with demonstration of 
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clinical benefit in inflammatory diseases involving joints, kidneys, and skin, and additional 
experience in pediatric patients with rare autoinflammatory diseases provides the rationale for 
evaluating baricitinib in pediatric patients with moderate-to-severe AD. 
Physicians with a specialty in dermatology and experience treating pediatric patients will 
participate as investigators in this clinical trial. 
3.2. Background  
Atopic dermatitis, also known as atopic eczema, is a common chronic relapsing highly 
symptomatic inflammatory skin disease.  Patients with AD may present with skin lesions that 
can be acute in presentation, with oozing, crusted, eroded vesicles, or papules on erythematous 
plaques.  Patients may also present with lesions that have a sub-acute appearance, with thick and 
excoriated plaques, or chronic appearance, with lichenified, slightly pigmented, excoriated 
plaques (Bieber 2010).  While clinical manifestations are overall similar in adults and pediatric 
patients, the localization and type of skin lesions differs slightly.  In infants, the first signs of AD 
usually emerge with eczematous, papulo-vesicular and patchy lesions localized to the cheeks.  In 
childhood, eczematous lesions typically involve flexural areas (ante-cubital fossae, neck, wrists, 
and ankles) and the nape of the neck, dorsum of the feet, and hands.  In adolescence and 
adulthood, flexural areas as well as head and neck will be typically involved with mostly 
lichenified plaques (Bieber 2010).  Atopic dermatitis causes pruritus attacks throughout the day 
and worsening at night, which is the primary source of morbidity in this disorder.  Pruritus often 
leads to an “itch-scratch” cycle (36% of patients report that they often or always scratch until 
their skin bleeds [Langenbruch et al. 2014]) that can further compromise the epidermal barrier 
and result in dry skin, microbial colonization, and secondary infections (Krakowski et al. 2008; 
Simpson 2012). 
In clinical practice, AD is classified based on a variety of clinical features, including severity of 
skin lesions and pruritus, and extent of disease (body surface area [BSA] involved).  Formal AD 
severity assessments used in clinical trials (e.g., Investigator’s Global Assessment [IGA], a 
severity scale commonly used in clinical trials to define mild, moderate, and severe disease that 
assigns a score of “2” for mild disease, “3” for moderate, and “4” for severe) are rarely used in 
clinical practice, which makes comparison of disease severity across different demographic 
groups difficult (Futamura et al. 2016).  In a population-based survey, approximately two-thirds 
of individuals with an empirical diagnosis of AD reported having moderate to severe symptoms 
(Hanifin et al. 2007).  Atopic dermatitis severity has been reported to be correlated with age in 
children, with older children being slightly more likely to have moderate to severe disease 
(Silverberg and Simpson 2014). 
Patients with AD (including children) experience higher rates of bacterial skin infection, with 
methicillin-resistant Staphylococcus aureus colonization occurring in approximately 90% of 
patients with severe AD versus 1% to 3% in the general population (Ong and Leung 2016).  
Viral skin infections can also occur in patients with AD.  Eczema herpeticum is one of the most 
frequent viral skin infections in patients with AD and occurs in approximately 3% of these 
patients (Ong and Leung 2016). 
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Patients with moderate-to-severe AD carry a heavy disease burden with medical and 
psychosocial abnormalities.  Atopic dermatitis can cause sleep disturbances in both adult and 
pediatric patients as a result of itching.  Sleep disturbances in AD are thought to be associated 
with nocturnal itch and scratching behavior (Mostaghimi 2008).  Similar to adults, health related 
quality of life (QoL) worsens in children with the severity of skin disease (Ben-Gashir et al. 
2004) and may reach or even exceed that experienced with many other chronic diseases of 
childhood, including asthma, epilepsy, diabetes, and chronic renal disease (Beattie and Lewis-
Jones 2006; Blome et al. 2016).  Children who experience irregular sleep are more likely to show 
problematic behaviors including anxiety and depression, social problems, attention problems, 
and delinquent or aggressive behaviors (Ben-Gashir et al. 2004; Yokomaku et al. 2008; Blome et 
al. 2016).  Another critical aspect of QoL in children with AD is difficulties with their peers.  
Lawson et al. (1998) showed that as much as 60% experienced bullying, 100% were teased, 30% 
had poor school attendance, and 54% experienced behavioral disturbances such as irritability, 
bad-temperedness, boredom, and being hurtful to other family members. 
Family QoL can also be severely impaired because of sleep deprivation by the affected child as 
well as disruption of school and social interactions (Su et al. 1997; Lawson et al. 1998; Leung 
2000; Ben-Gashir et al. 2004).  Lawson et al. (1998) suggests that 74% of parents experienced a 
general burden of extra care and that 71% expressed feelings of guilt, exhaustion, frustration, 
resentment, and helplessness. 
There are no known differences in the aetiology of AD between adults and children, as the vast 
majority of patients (85%) with adult AD are diagnosed before the age of 5 years (Bieber 2010).  
The underlying cause of AD is not yet completely understood.  The importance of genetic factors 
must be taken into account because a positive parental history is the strongest risk factor for AD 
in children.  The incidence rate of AD in children is doubled if one parent has the disease and is 
tripled if both parents have the disease (Bieber 2010).  Loss of function mutations in filaggrin 
(filament aggregation protein) gene, 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 (Irvine et al. 2011). 
At a cellular level, AD is characterized by excessive T-cell activation caused by genetic and 
environmental factors, leading to significant skin infiltration by T-cells and dendritic cells.  The 
cytokine TSLP is thought to act as a master switch that triggers the initiation and maintenance of 
AD (Moniaga et al. 2013; Ziegler et al. 2013).  In addition to directly inducing itch by activating 
sensory neurons in the skin (Wilson et al. 2013), 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; Zhong et al. 2014; Divekar and Kita 
2015).  While the fundamental pathophysiology with excessive T-cell activation is similar in 
adults and children, recent literature suggests that in early pediatric AD, the Th2 imbalance may 
be confined to skin-homing (cutaneous lymphocyte antigen–positive) T-cell subsets, while in 
adults T-cell activation extends into systemic/cutaneous lymphocyte antigen–negative and CD8+ 
T cells, as well as into IL-22–producing T-cells (Czarnowicki et al. 2015, Werfel et al. 2016a).  
Thymic stromal lymphopoietin and other key cytokines involved in AD pathogenesis, such as 
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IL-13, IL-5, IL-4, IL-22, and IL-31, signal through receptors associated with intracellular JAK 
signal transducers and activators of transcription activation and are anticipated to be modulated 
by baricitinib treatment (Clark et al. 2014).  In addition, several cytokines (e.g., TSLP, IL-33) 
can directly activate pruritogenic neurons to mediate itch, and these pruritogenic cytokines 
utilize receptors that can be attenuated by JAK1 and JAK2 inhibitors (Oetjen et al. 2017). 
The overall prevalence of AD among children and adolescents is approximately 10% to 13% 
(Augustin et al. 2015; Shaw et al. 2011; Silverberg and Simpson 2014).  A recent analysis of data 
from 293,181 children up to 18 years of age from a German health insurance database showed a 
prevalence of 10% for a diagnosis of atopic eczema (Augustin et al. 2015).  Epidemiological data 
from a children’s health national survey in the US based on study of a nationally representative 
sample of 91,642 children age 0 to 17 years showed that the overall prevalence of childhood 
eczema was 13%, with 67% having mild disease, 26% having moderate disease, and 7% having 
severe disease (Silverberg and Simpson 2014).  These data suggest that AD severity is correlated 
with age in children, with older children being slightly more likely to have moderate to severe 
disease.  It has been estimated that 2% of pediatric patients with atopic eczema/dermatitis have 
severe disease that does not respond to topical anti-inflammatory drugs or UV light treatment 
(McAleer et al. 2012).  
3.3. Benefit/Risk Assessment  
In the baricitinib Phase 2 study in moderate-to-severe AD, Study JAHG, baricitinib doses of 2- 
and 4-mg showed early improvement in both physician- and patient-reported signs and 
symptoms of AD, including improvement in skin inflammation, itch, sleep disruption, and 
quality of life.  For a summary of the Phase 2 Study (JAHG) efficacy data, see Section 5.5 
(Justification for Dose). 
Serious infections, venous thromboembolic events, hepatotoxicity, and fetal malformations were 
identified as important potential risks with baricitinib in RA studies.  Although infections were 
seen in about half of the study population exposed to baricitinib in the RA program, only 3.6% of 
patients reported a serious treatment-emergent infection, and rates were similar in both 
baricitinib- and placebo-treated patients.  In the Phase 2 AD study, approximately 25% of 
patients treated with the 4-mg dose experienced a treatment-emergent adverse event (TEAE) of 
infection and infestation, compared to 20% of patients treated with placebo.  There were no 
venous thromboembolic events (VTEs), serious infections, opportunistic infections, or herpes 
zoster infections reported during the treatment period in the AD Phase 2 study.  The nonserious 
infections for baricitinib noted in the RA program (upper respiratory tract infections, herpes 
zoster, and herpes simplex) are readily diagnosed, manageable, and typically resolve without 
long-term sequelae.  It is recommended that where indicated, herpes zoster vaccination will be 
offered to patients prior to receiving baricitinib, and infections have generally been mild to 
moderate, localized, and without long-term problems.  It is important to consider that in AD, 
patients are at an increased risk for skin infections due to disruption of the skin barrier, which is 
worsened by occurrence of eczematous skin lesions and scratching (Krakowski et al. 2008).  In 
the Phase 2 study of baricitinib, there was no increase in the occurrence of skin infections with 
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baricitinib, likely due to improvements observed in skin lesions and itch.  Exclusion criteria have 
been added to the protocol to limit enrollment of patients who are at increased risk of infection.  
Cases of hepatotoxicity have not been identified with baricitinib use, but increases in alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin have been seen in 
RA patients.  Most of these increases improved with continued use or temporary discontinuation 
of baricitinib with no long term effects.  Exclusion criteria to not enroll patients with liver failure 
or increased liver analytes, appropriate monitoring of hepatic analytes and discontinuation 
criteria have been included in the protocol.  Fetal malformations were reported in toxicology 
studies at higher doses than what is used in human patients.  Only a small number of patients 
have become pregnant in baricitinib clinical trials, and there have been no reports of fetal 
malformations in these pregnancies.  In current study protocols, pregnant patients are excluded 
from entry, contraceptive use is defined in the inclusion criteria, and patients who become 
pregnant are discontinued from the trial.  
Venous thromboembolic events (VTEs) have been determined to be an important potential risk 
for baricitinib.  There was a numerical imbalance in reports of VTEs in the 24-week placebo-
controlled period of the Phase 3 trials of patients with RA.  Available evidence does not establish 
a causal association.  The exposure-adjusted incidence rate of VTE for baricitinib-treated RA 
patients over long-term exposures was similar to the background rates published in the literature 
for the target population.  There was no pattern of increased or decreased risk during long-term 
exposures, and cases observed with baricitinib were confounded by one or more recognized risk 
factors for VTE.  Venous thromboembolic event risk can be managed through risk mitigation 
strategies.  Exclusion and discontinuation criteria have been added to the protocol to limit 
participation of patients who are at increased risk of VTE.  Therefore, in the context of the 
cumulative knowledge, the benefit/risk balance for baricitinib for the treatment of adult patients 
with moderate-to-severe AD is assessed to be favorable.  The overall safety profile in the 
pediatric patients with rare auto-inflammatory conditions participating in the JAGA expanded 
access program did not identify any new safety signals beyond those identified in the Phase 3 
studies in adult patients with RA for the range of doses tested:  from 1- to 12-mg/day.  Children 
generally carry less medical disease burden than adults (i.e., children are generally more healthy 
than adults and they do not have other medical conditions that occur with aging such as diabetes, 
heart disease, arthritis, etc.); therefore, they will be at a lower risk for some of the adverse events 
(AEs) related to comorbidities observed in RA studies, and are not anticipated to be at any higher 
risk of AE potentially associated with baricitinib.  Thus it is expected that the benefit/risk 
balance for baricitinib for the treatment of pediatric patients with moderate-to-severe AD would 
be similar to adults.  
Phase 3 studies of adult patients with AD have been completed; please refer to the Investigator’s 
Brochure (IB) for more information on efficacy and safety in adult patients with AD.  In 
summary, the primary objective (IGA score for AD of clear or almost clear [IGA 0,1]) as well as 
most other secondary measures were met for the 4-mg dose in completed studies.  The 2-mg 
dose met the primary endpoint in 2 of 3 completed studies and demonstrated clinically relevant 
efficacy across a range of secondary endpoints across the various studies.  The 1-mg dose 
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demonstrated efficacy on some endpoints but did not show consistent efficacy across the 
completed studies where it was included.  Safety observations in adult patients with AD from 
long-term extensions up to 2 years in duration have not revealed any new safety signals, and the 
safety profile for baricitinib in adult patients with AD remains generally consistent with the 
known safety profile in RA.  Acne and increased creatine phosphokinase were reported with 
greater frequency in adult AD patients than RA patients.  
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated AEs of baricitinib are to be found in the IB. 
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4. Objectives and Endpoints  
Table JAIP.3 shows the objectives and endpoints of the study. 
Table JAIP.3. 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary Objective for Double-blind Treatment 
Period 
 
To demonstrate the superiority of each dose of 
baricitinib versus placebo in the treatment of 
patients with moderate-to-severe AD. 
 
 
Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at Week 16 
 
Primary Objective for PK lead-in Period 
 
To assess whether baricitinib exposure in 
pediatric patients receiving baricitinib high 
dose once daily is comparable to the exposure 
in adults receiving baricitinib 4-mg once 
daily. 
 
Comparability will be assessed using non-
compartmental methods (e.g., AUC and Cmax) 
Key Secondary Objectives 
These are prespecified objectives that will be adjusted 
for multiplicity 
 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week double-blind placebo-controlled 
treatment period as measured by improvement 
in signs and symptoms of AD. 
 
Proportion of patients achieving EASI75 at 
16 weeks 
 
Proportion of patients achieving EASI90 at 
16 weeks 
 
Mean change from baseline in EASI score at 
16 weeks 
 
Proportion of patients achieving SCORAD75 
at 16 weeks 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week double-blind placebo-controlled 
treatment period as assessed by 
patient-reported outcome measures.  
 
Proportions of patients achieving a 4-point 
improvement in Itch NRS at 1 week, 2 weeks, 
4 weeks, and 16 weeks for patients ≥10 years 
old 
Other Secondary Objectives 
These are prespecified objectives that will not be 
adjusted for multiplicity. 
 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week double-blind placebo-controlled 
period as measured by physician-assessed 
signs and symptoms of AD. 
 
Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at Week 4 
 
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 
 
Mean percent change from baseline in 
SCORAD at 16 weeks 
 
Proportion of patients achieving SCORAD90 
at 16 weeks 
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Objectives 
Endpoints 
 
Mean percent change from baseline in EASI 
score at 16 weeks 
 
Mean change from baseline in BSA affected 
at 16 weeks 
 
Proportion of patients developing skin 
infections requiring antibiotic treatment by 
Week 16 
 
To compare the efficacy of baricitinib high, 
medium, or low dose to placebo in AD during 
the 16-week, double-blind, placebo-controlled 
treatment period as assessed by 
patient-reported outcome/QoL measures. 
 
Mean number of days without use of 
background TCS over 16 weeks 
 
Mean gram quantity of TCS used over 16 
weeks (tube weights) 
 
Mean change from baseline in Itch NRS at 1 
week, 4 weeks and 16 weeks for patients ≥10 
years old 
 
Mean percent change from baseline in Itch 
NRS at 1 week, 4 weeks and 16 weeks for 
patients ≥10 years old  
 
Mean change in the PRISM at 1 week, 
2 weeks, 4 weeks, and 16 weeks for patients 
<10 years old 
 
Mean change from baseline in the total score 
of the POEM at 16 weeks  
 
Mean change in PGI-S-AD scores at 16 weeks 
 
Mean change from baseline in the PROMIS-
pediatric depression at 16 weeks  
 
Mean change from baseline in the PROMIS-
pediatric anxiety at 16 weeks 
 
Mean change from baseline in DFI at 16 
weeks 
 
Mean change in CDLQI/IDQOL scores at 16 
weeks 
 
Mean change in WPAI-AD-CG scores at 
16 weeks 
 
Mean change in EQ-5D-Y scores at 16 weeks 
 
Mean change from baseline in the score of 
Item 2 of the ADSS at 1 week and 16 weeks 
for patients ≥10 years old 
 
Mean change from baseline in Skin Pain NRS 
at 16 weeks for patients ≥10 years old 
 
To assess the patient acceptability and 
palatability of baricitinib tablets and oral 
suspension.  
 
Assessment of tablet or oral suspension 
product acceptability and palatability during 
the Open-label PK Lead-in period 
 
To characterize the pharmacokinetic profile of 
the baricitinib in pediatric patients with AD. 
 
Population PK Analysis based on sparse 
sampling over 16 weeks (Study Period 3) with 
secondary endpoints including Cmax, AUC, 
and t1/2  
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Objectives 
Endpoints 
 
To evaluate the potential effects of baricitinib 
on the cellular and humoral immune system. 
 
Change of IgG titers from pre-vaccination to 
4 weeks and 12 weeks post vaccination in 
patients eligible for vaccination with tetanus, 
diphtheria, and pertussis (TDaP) and/or 
pneumococcal conjugate vaccine according to 
local guidelines 
 
To assess efficacy of baricitinib during 
longer-term treatment. 
 
Proportion of patients achieving IGA of 0 or 1 
with a ≥2-point improvement at 1 year 
 
Proportion of patients achieving EASI75 at 
1 year 
 
Proportion of patients achieving SCORAD75 
at 1 year 
 
To assess growth and bone safety of 
baricitinib during longer-term treatment. 
 
Mean changes in growth (height and weight), 
growth velocity, and bone age over the course of 
treatment during the long-term extension treatment 
period  
Tertiary/Exploratory Objectives 
 
 
Frequency of patient-reported “no itch” (Itch NRS score = 0) days from daily diaries from Week 12 to 
Week 16 
 
Frequency of patient-reported “no pain” (Skin Pain NRS score = 0) days from daily diaries from 
Week 12 to Week 16 
 
Time to achieve a 4-point improvement in Itch NRS  
 
Mean change from baseline in the score of Item 1 of the ADSS at 1 week and 16 weeks  
 
Mean change from baseline in the score of Item 3 of the ADSS at 1 week and 16 weeks 
 
To evaluate changes from baseline in IgE levels during the study 
 
To evaluate changes from baseline in eosinophil levels during the study 
 
To characterize baricitinib pharmacokinetics in the AD population and explore relationships between 
baricitinib exposure and study endpoints 
 
Assessment of efficacy outcomes in patients who choose to take a voluntary drug interruption (drug 
holiday) during Study Period 4 
 
Number of patients able to maintain control of AD signs and symptoms without use of TCS 
 
Proportion of patients achieving IGA of 0 or 1 with a ≥2-point improvement at 2, 3, 4, and 5 years 
during long-term extension 
 
Proportion of patients achieving EASI75 at 2, 3, 4, and 5 years during long-term extension 
 
Proportion of patients achieving SCORAD75 at 2, 3, 4, and 5 years during long-term extension 
Abbreviations:  AD = atopic dermatitis; ADSS = Atopic Dermatitis Sleep Scale; AUC = area under the 
concentration curve; BSA = body surface area; CDLQI = Children’s Dermatology Life Quality Index; 
Cmax = maximum concentration; DFI = Dermatology Family Impact; EASI = Eczema Area and Severity Index; 
EQ-5D-Y = the European Quality of Life–5 Dimensions–Youth; IDQOL = Infant’s Dermatitis Quality of Life 
Index; IGA = Investigator’s Global Assessment; IgE = immunoglobulin E; IgG = immunoglobulin G; 
NRS = numeric rating scale; PK = pharmacokinetic; QoL = quality of life; PGI-S-AD = Patient Global 
Impression of Severity–Atopic Dermatitis; POEM = Patient-Oriented Eczema Measure; 
PRISM = Parent-Reported Itch Severity Measure; PROMIS = Patient-Reported Outcomes Measurement 
Information System; t1/2 = half-life; TCS = topical corticosteroids; SCORAD = SCORing Atopic Dermatitis; 
WPAI-AD-CG = Work Productivity and Activity Impairment:  Atopic Dermatitis – Caregiver. 
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5. Study Design  
5.1. Overall Design  
Study I4V-MC-JAIP (JAIP) is a Phase 3, multicenter, randomized, double-blind, 
placebo-controlled, parallel-group, outpatient study evaluating the pharmacokinetics, efficacy, 
and safety of baricitinib compared with placebo in pediatric patients with moderate-to-severe 
AD.  The study is divided into 5 periods, a 5-week Screening period, a 2-week Open-label PK 
lead-in period, a 16-week Double-Blind Treatment period, an up to 5-year Long-term Extension 
period, and a 4-week Post-treatment Follow-up period.  While the primary objective of this study 
is to investigate whether baricitinib is superior to placebo in the treatment of the signs and 
symptoms of AD in pediatric patients, an important secondary objective of the study is to assess 
the ability of baricitinib to reduce or eliminate the need for use of topical antiflammatory agents, 
the use of which is frequently a concern among parents and caregivers of pediatric AD patients. 
Approximately 465 patients 2 to <18 years of age who have responded inadequately to or who 
are intolerant to topical therapy will be enrolled into the study, of which, approximately 
25 patients will be enrolled into the Open-label PK Lead-in period (Study Period 2).  The 
remaining patients (at least 440 patients) will be randomized at a 1:1:1:1 ratio to receive placebo 
QD, baricitinib low dose QD, baricitinib medium dose QD, or baricitinib high dose QD 
(110 patients in each treatment group with at least 320 patients 10 to <18 years old and at least 
120 patients 2 to <10 years old).   
The original protocol was written as a monotherapy study (including TCS washout), and the 
open-label PK Lead-in period (Study Period 2) will be conducted as such.  Protocol amendment 
JAIP(a) permits the use of background low- and medium-potency TCS, and all patients 
participating in Study Period 3 (Double-blind treatment) will follow this for subsequent 
amendments including the amendment, JAIP(b). 
Patients will be stratified at randomization according to disease severity (IGA 3 vs. 4) and 
geographic region (if the planned country allocation justifies).  Definitions of geographic regions 
and plan for analysis by region will be described in the statistical analysis plan (SAP). 
Study governance considerations are described in detail in Appendix 3. 
5.1.1. Period 1:  Screening  
The duration of the Screening period is between 8 and 35 days prior to Visit 2 (Week 0).  At 
Visit 1, the patient or parent/legal guardian will sign the informed consent form (ICF) prior to 
any study assessments, examinations, or procedures being performed.  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 have the skin test read.   
Patients Participating in Study Period 2 (PK Lead-in) 
Patients who will participate in the open-label PK lead-in (Study Period 2) will be required to 
wash out of prior AD treatments as described in Section 6.1 (Study Population) and Section 7.7.    
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Patients Participating in Study Period 3 (Double-blind treatment) 
Prior to randomization (Study Period 3), systemic treatments for AD will be washed out for 
4 weeks.  Certain topical treatments (not including emollients) will be discontinued prior to Visit 
2 as described in Section 6.1 (Inclusion Criteria [6 c]) and Section 7.7.  Sponsor-provided low- 
and medium-potency TCS will be given to patients at Visit 1, and patients will discontinue use of 
other TCS medications and begin use of the Sponsor-provided TCS medications as prescribed by 
the investigator (as clinically indicated).  During the screening period, TCNIs (e.g., tacrolimus 
and pimecrolimus) or topical PDE-4 inhibitor (i.e., crisaborole, where approved) are permitted in 
place of TCS as 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.). 
All Patients 
Patients will be required to use emollients daily during the 14 days preceding Visit 2 and 
throughout the study.  If patients have been using emollients daily at the time of screening, then 
those cumulative days can be utilized to meet inclusion criterion [7].  Patients will receive a daily 
reminder via the daily diary to apply emollient.  Additionally, collection of data through daily 
diaries will be required throughout the Screening period.  The baseline for the daily patient-
reported outcome (PRO) will be the average score of the 7 days prior to Visit 2; thus the 
minimum screening window was set at 8 days.  
Investigators should review the vaccination status of their patients to assess that patients are up 
to date with immunizations following the local guidelines for vaccination of pediatric patients 
<18 years of age with vaccines intended to prevent infectious disease prior to entering patients 
into the study.  Typhoid and Bacillus Calmette-Guérin (BCG) live vaccines are not permitted 
within 12 weeks of Visit 2.  If a patient received a live vaccine within 28 days prior to Visit 2 or 
intends to receive a live vaccine during Study Period 2 or 3, the patient is not eligible for the 
study.  If patients become eligible for vaccination with tetanus, diphtheria, and pertussis (TDaP) 
and/or pneumococcal conjugate vaccine during the study according to local recommended 
schedules of vaccination, antibody titers to the vaccine will be evaluated pre-immunization and 
at 4 and 12 weeks post-immunization.  A primary immune response will be assessed in patients 
who have never received TDaP or pneumococcal conjugate vaccines previously, and 
secondary/booster responses will be assessed if the patients have previously received the 
vaccines. 
Patients who meet all of the inclusion and none of the exclusion criteria (Sections 6.1 and 6.2) 
will continue to Visit 2. 
5.1.2. Period 2:  Open-label PK lead-in  
The Open-label PK Lead-in period will evaluate if exposure to baricitinib high dose in pediatric 
patients is comparable with baricitinib exposure in adults.  Patients will receive oral baricitinib at 
a fixed high dose by age group QD for approximately 2 weeks.  The 2-week, open-label PK 
lead-in will include serial PK sampling so that baricitinib exposure can be evaluated in this 
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population.  Enrollment will be staggered by age group (10 to <18 years, 6 to <10 years, and 2 to 
<6 years), with older groups enrolling before younger groups.  
Approximately 25 patients will be enrolled into the PK lead-in with at least: 
 Oldest age group:  15 patients 10 to <18 years old including at least 5 patients in each of 
the following age groups:   
o 10 to <12 years 
o 12 to <15 years 
o 15 to <18 years 
 Middle age group:  at least 5 patients 6 to <10 years old, and  
 Youngest age group:  at least 5 patients 2 to <6 years old 
At Visit 2 (Week 0, baseline), study eligibility for each patient will be reviewed, based on all 
inclusion and exclusion criteria (Sections 6.1 and 6.2) and laboratory test results.  Patients who 
meet all criteria will proceed in the study and begin open-label treatment in the PK lead-in period 
(Visits 2, 3, and 4). 
After patients in the oldest age group (10 to <18 years old) have completed the 2-week, 
open-label PK lead-in, an analysis will be conducted to evaluate the PK and safety profiles and 
confirm baricitinib exposure and dosing prior to any enrollment of patients in this age group into 
the Double-blind Treatment period.   
After the analysis of the PK data for the patients in the oldest age group (10 to <18 years old) has 
completed, the middle age group (6 to <10 years old) will begin enrollment into the PK lead-in 
period.  After analysis of the PK lead-in data for the patients in the middle age group (6 to 
<10 years old) has completed, the youngest age group (2 to <6 years old) will begin enrollment 
into the PK Lead-in period.  Enrollment of patients in the middle and youngest age groups 
directly into the Double-blind Treatment period will begin only after analysis of the PK lead-in 
data for the specific age group has been completed.  
After completing the PK lead-in (Visit 4), patients may proceed to the Long-term Extension 
period (Visit 9) 2 weeks after completing Visit 4 and continue to receive open-label baricitinib at 
the same dose they received in the PK lead-in. 
The study design for the Open-label PK Lead-in period is illustrated in Figure JAIP.1.  A 
Schedule of Activities showing required procedures for the open-label PK lead-in is included in 
Section 2.  The PK sampling schedule is described in Section 9.5.  Patients participating in the 
PK lead-in will follow the procedures shown in the Schedule of Activities (Section 2) for 
Visits 2, 3, and 4 with serial PK samples collected as described in Section 9.5.  A total of 7 PK 
samples will be collected during the PK lead-in period (2 PK samples will be collected at Visit 2, 
and 5 PK samples will be collected during the 2 weeks following Visit 2). 
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Abbreviations:  AD = atopic dermatitis; PBPK = Physiologically Based Pharmacokinetic; PK = pharmacokinetic; 
QD = once daily; V = visit; W = week.  
A 
Based on PBPK modelling results, the high dose for patients 10 to <18 years old is 4 mg, and the high dose 
for patients 2 to <10 years is 2 mg.  
Figure JAIP.1. 
Illustration of study design for Clinical Protocol I4V-MC-JAIP (PK 
Lead-in, Study Period 2).  
5.1.3. Period 3:  Double-blind Placebo-Controlled Treatment Period  
General enrollment into Study Period 3 will begin for an age group only after analysis of the PK 
lead-in data for the specific age group confirms appropriate dose selection.  Patients who 
participated in the PK lead-in will not participate in Study Period 3. 
Patients who will participate in the double-blind treatment period (Study Period 3) will continue 
using Sponsor-provided low- and medium-potency TCS as clinically indicated and determined 
by the investigator.  At Visit 2 (Week 0, baseline), study eligibility for each patient will be 
reviewed, based on all inclusion and exclusion criteria (Sections 6.1 and 6.2, respectively) and 
laboratory test results.  Patients who meet all of the inclusion criteria and none of the exclusion 
criteria will proceed to randomization and begin the 16-week double-blind, placebo-controlled 
treatment period (Figure JAIP.2).  
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At Visit 2, after laboratory samples are collected and all assessments are completed, patients will 
take the first dose of investigational product (IP) at the clinic and PK samples will be drawn 
15 minutes and 1 hour postdose.  Pharmacokinetic sampling and the related timing of dosing for 
IP for each visit are detailed in Section 9.5. 
Patients will be randomized at a 1:1:1:1 ratio into 1 of the 4 treatment groups (placebo QD, 
baricitinib low dose QD, baricitinib medium dose QD, or baricitinib high dose QD).  
Investigational product will be administered daily for 16 weeks (treatment period Visits 2 
through 8).  All patients will be required to use emollients daily.  Daily diaries will continue to 
be utilized throughout the treatment period.  The use of low- and medium-potency TCS, TCNIs, 
and phosphodiesterase type 4 (PDE-4) inhibitor for the treatment of AD is allowed as 
background treatment as described in Section 7.7.1.  High- and ultra-high-potency TCS and 
systemic therapies may be used as rescue treatment during Study Period 3 (details of rescue 
therapy and criteria are included in Section 7.7.5).  Assessments of disease severity will be 
performed by the investigator at all study visits including unscheduled and early termination 
visits (ETVs). 
The primary efficacy endpoint and final visit in the treatment period will be at Week 16 (Visit 8).  
Patients who complete through the Week 16 study visit will be eligible to continue in the 
Long-term Extension period for up to 5 additional years of treatment. 
If a patient discontinues IP for any reason, the patient should remain in the study through 
Week 16 (Visit 8).  If the patient refuses and wishes to withdraw consent, an ETV should be 
performed as soon as logistically possible. 
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Abbreviations:  PK = pharmacokinetic; QD = once daily; V = visit; W = week. 
A 
Dosing for the Double-blind Treatment period will be confirmed through the PK lead-in.  The anticipated 
daily baricitinib doses for patients 10 to <18 years old are 4 mg, 2 mg, and 1 mg.  The anticipated daily baricitinib 
doses for patients 2 to <10 years old are 2 mg, 1 mg, and 0.5 mg.   
Figure JAIP.2. 
Illustration of study design for Clinical Protocol I4V-MC-JAIP 
(Double-Blinded Treatment, Study Period 3).  
5.1.4. Period 4:  Long-term Extension Treatment Period  
PK Lead-in Patients: 
Patients participating in the PK lead-in period (Study Period 2) may proceed to the Long-term 
Extension period (Visit 9) 2 weeks after completing Visit 4 and continue to receive open-label 
baricitinib at the same dose they received in the PK lead-in.  Patients may continue in the long-
term extension for up to an additional 5 years (Figure JAIP.3).   
Non-PK Lead-in Patients: 
Patients who participate in the Double-blind Treatment period (Study Period 3) and complete 
through Week 16 (Visit 8) will be eligible to continue in the Long-term Extension period for up 
to 5 additional years of treatment (Figure JAIP.3).  At Visit 8 (primary endpoint and end of the 
double-blind period), patients will be transitioned into the long-term extension treatment period 
as follows: 
 Patients randomized to Double-blind Treatment who have achieved a response of IGA 0, 
1, or 2 at Visit 8 (Week 16) without requiring rescue with topical treatments or systemic 
treatments during Study Period 3 will continue on the Double-blind Treatment to which 
they were randomized at Visit 2 (Week 0). 
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 Patients randomized to Double-blind Treatment who have not achieved a response (i.e., 
IGA of ≥3) or who have required rescue with topical treatments (i.e., high-/ultra-high-
potency TCS) or systemic treatments during Study Period 3 will be transitioned to open-
label baricitinib at the high dose for their age group. 
All Patients: 
During Study Period 4, patients are allowed to use TCS (all potencies), TCNI, and/or a PDE-4 
inhibitor (e.g., crisaborole) as background treatments with IP if they experience worsening or 
lack of control of their AD. 
During the first year of the extension treatment, use of background TCS, TCNI, and PDE-4 
inhibitors is allowed as described in Section 7.7.2.  During Study Period 4, for patients on 
double-blind treatment whose IGA worsens to 3 or 4 and who are unable to recapture an IGA 
response of 0, 1, or 2, despite the use of emollients and TCS, the patient may be transitioned at 
the discretion of the investigator to open-label baricitinib at the high dose for their age group.  
After the first year of the extension treatment period, treatment and transition to open-label 
baricitinib will continue as in the first year; however, patients will be allowed to voluntarily 
interrupt IP treatment after Visit 15 provided they continue to complete all other study visit 
procedures per protocol.  In addition to investigator discretion and patient/parent agreement, at 
least 1 of the response criteria described below must be met in order to initiate a voluntary 
interruption of the IP:  
 IGA ≤2 
 EASI75 or better (≥75% reduction in Eczema Area and Severity Index [EASI] from 
Visit 2) 
 <3% BSA involvement 
Voluntary interruption of treatment (drug holiday) is an approach to long-term treatment that 
may be more representative of actual treatment practice, where patients may use baricitinib 
intermittently (i.e., “treat when needed”) rather than on a continuous basis.  The IP may be 
resumed (at the same dose) after a voluntary interruption if symptoms worsen based on 
investigator assessment of benefit/risk and patient/parent agreement.  The symptoms leading to 
resumption of the IP will be captured on the case report form (CRF). 
During the long-term extension live vaccines (e.g., booster immunization with attenuated vaccine 
measles, mumps, and rubella [MMR] or varicella zoster virus [VZV]) may be considered if they 
are essential based on the local guideline and/or in the opinion of the investigator and with 
appropriate interruption of baricitinib treatment prior to and after the live vaccine (see 
Section 7.7.4). 
The benefit/risk profile will be reassessed throughout the study and patients may be discontinued 
at any time.  In particular, during the long-term extension period, the investigators should 
continue to assess the benefit/risk profile of patients to remain in the trial after Week 16.  For a 
patient having safety and tolerability issues, or one who is not achieving adequate treatment 
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response, investigators should use clinical judgment on whether to continue or discontinue 
patient participation in the study. 
The total duration of this study is expected to last until the anticipated approval of baricitinib in 
this indication; however, given that the benefit risk in AD had not been demonstrated in pivotal 
Phase 3 adult studies at the time of the original protocol approval, the study duration had been 
initially set at 2 years.  Data from the Phase 3 AD studies in adults and initial data from the 
current study (JAIP) have now indicated a favorable benefit/risk; therefore, this protocol has 
been amended to further extend the duration of Study JAIP for a total treatment period of up to 
5 years or until the anticipated approval and availability of baricitinib for the treatment of AD.  
At Visit 27, patients eligible for treatment with a commercially available, approved, systemic 
JAK or biologic therapy should be discontinued from study treatment; this will be considered the 
final visit of Study Period 4. For patients 12 years of age and older at the time of Visit 27, Visit 
27 will be the final treatment visit unless prior documented written sponsor’s approval has been 
obtained to allow the patient to continue on study treatment.  Patients younger than 12 years of 
age at the time of Visit 27 who are not eligible for commercially available, approved, systemic 
JAK or biologic therapies may be eligible to continue in Study Period 4 beyond Visit 27.  The 
investigator must provide documentation supporting the need for continued treatment under the 
study protocol and obtain sponsor’s written approval prior to patient completing Visit 27.   
Patients <12 years of age should be discontinued from study treatment at the first study visit after 
meeting eligibility for an approved systemic JAK or biologic alternative. The investigator should 
discuss post-study treatment options with the patient prior to Visit 27 to ensure continuity of 
patient care. 
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Abbreviations:  IP = investigational product; PK = pharmacokinetic; SP = study period; TCS = topical 
corticosteroid; V = visit; W = week. 
Figure JAIP.3. 
Illustration of study design for Clinical Protocol I4V-MC-JAIP 
(Long-term Extension, Study Period 4).  
5.1.5. Period 5:  Post-Treatment Follow-Up  
Patients who complete Study Period 2 through Visit 4 (Week 2) and patients who complete 
Study Period 3 through Visit 8 (Week 16) and do not enter the long-term extension study will 
have a post-treatment follow-up visit (Visit 801) approximately 28 days after the last dose of IP.  
Patients who complete Study Period 4 through Visit 31 will have a post-treatment follow-up visit 
(Visit 801) approximately 28 days after the last dose of IP. 
Patients who have received at least 1 dose of IP 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 IP. 
Patients who have discontinued IP but remain in the study for more than 28 days without IP will 
have an ETV if they chose to discontinue early; however, a separate follow-up visit (V801) is not 
required. 
Patients should not initiate new systemic AD treatment during this period.  However, if patients 
or investigators must initiate treatment, patients should complete an unscheduled visit prior to the 
first dose of the new therapy. 
5.2. Number of Participants  
Approximately 465 patients will be enrolled into this study.  
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Approximately 25 patients will be enrolled into the open-label PK lead-in (at least 15 patients 
aged 10 to <18 years old and at least 10 patients aged 2 to <10 years old). 
Approximately 440 patients will be enrolled/randomized into the Double-blind Treatment period 
(with at least 320 patients aged 10 to <18 years old and at least 120 patients aged 2 to <10 years 
old.  
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 pediatric patients with moderate to severe AD who have a history of 
inadequate response or intolerance to existing topical therapies and for whom a systemic 
treatment such as baricitinib may, therefore, be appropriate. 
During the Screening period (Period 1), a washout of systemic and certain topical treatments for 
AD will be incorporated prior to randomization to minimize confounding effects due to 
background treatment.  The PK lead-in (Period 2) will confirm that the baricitinib exposure at the 
high dose for each pediatric AD age group is comparable to the 4-mg dose exposure in adults 
with AD.  The double-blind, placebo-controlled treatment period (Period 3) is designed to 
minimize bias in the evaluation of the efficacy and safety of 3 baricitinib doses, relative to 
placebo, through 16 weeks of treatment.  Patients who will participate in the double-blind 
treatment period (Study Period 3) will be allowed to continue treatment with TCS.  Sponsor-
provided low- and medium-potency TCS will be given to patients at Visit 1, and patients will use 
the TCS medications as prescribed by the investigator (as clinically indicated).  
Topical corticosteroids are the first-line anti-inflammatory treatment in adult and pediatric 
patients with AD, even for patients treated with systemic treatments.  For this reason, this study 
will assess the efficacy of baricitinib in combination with background low- to medium-potency 
TCS including a TCS run-in during the screening period from Visit 1 to Visit 2.  In consideration 
of the disease severity, all patients in Study Period 3 (double-blind treatment) are eligible for 
rescue to higher potency TCS.  Investigators are allowed to rescue patients who are experiencing 
unacceptable or worsening symptoms of AD.  Once rescue medication is used, the patient will be 
determined to be a nonresponder for the 16-week primary analysis (see Section 10.3.1). 
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).  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 (e.g., moderate to severe).  The scale that will be 
used in this trial, the validated Investigator’s Global Assessment of Atopic Dermatitis 
(vIGA-AD, referred to throughout the protocol as IGA), has been developed internally and 
assesses AD severity using a 5-point scale. 
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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 
from previous studies in another inflammatory skin condition. 
The long-term extension (Period 4) should offer additional opportunity for patients to receive 
benefit from treatment and provide additional long-term safety and tolerability information. 
After the first year of the extension treatment period, patients will be allowed to voluntarily 
interrupt IP treatment provided they continue to complete all other study visit procedures per 
protocol.  This voluntary interruption (drug holiday) based on response, investigator discretion, 
and patient/parent agreement is an approach to long-term treatment that may be more 
representative of actual treatment practice, where patients may use baricitinib intermittently (i.e., 
“treat when needed”) rather than on a continuous basis.  Investigational product may be resumed 
after a voluntary interruption if symptoms worsen. 
The Post-treatment Follow-up period (Period 5) is for safety monitoring after the patient has 
been off IP for approximately 28 days. 
5.5. Justification for Dose  
The PK of baricitinib have been characterized in adults and are linear and time-independent 
across a wide dose range.  Renal elimination is the principal mechanism for baricitinib’s 
clearance through glomerular filtration and active secretion via OAT3, Pgp, BCRP, and MATE2-
K.  Baricitinib is expected to behave similarly between pediatrics and adults, based on the 
ADME of baricitinib and Physiologically Based Pharmacokinetic (PBPK) modelling (PBPK 
program Simcyp®).  Physiologically Based Pharmacokinetic modelling was used to predict 
exposures and set the high dose for pediatric age cohorts within the age range to be studied (2 
years to <18 years).  Considering safety and tolerability, the high dose in each pediatric age 
group will be set to the dose that produces comparable exposure to the highest effective 
baricitinib dose tested in the adult Phase 2 AD study (4-mg).  Lower doses at ½ and ¼ the high 
dose will be studied to cover the dose range where clinical response can be anticipated (similar 
ratios of the high dose as being studied in the adult Phase 3 AD studies, [i.e., 4, 2 and 1 mg]).  
Older pediatric population (10 to <18 years) 
Based on PBPK modelling, it is anticipated that a 4-mg dose will produce comparable exposure 
in pediatric patients (10 years to <18 years old) and adults with AD.  Based on a 4-mg dose, the 
model-predicted area under the concentration curve (AUC) and the maximum concentration 
(Cmax) in 10 to <18 year old patients with AD is within the 5th and 95th percentiles of the AUC 
and Cmax in adult patients with AD.  Therefore the maximum dose in older pediatric patients 10 
to <18 years old is proposed to be 4-mg with medium and low doses of 2-mg and 1-mg, 
respectively (same doses being tested in the ongoing adults Phase 3 AD studies).   
In the baricitinib Phase 2 AD Study in adults (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.  
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However, 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 the 2-mg dose, particularly 
in the subgroup of patients with baseline EASI scores ≥16.  Although in Study JAHG the 4-mg 
dose seemed to perform better than the 2-mg dose on more stringent endpoints, on other 
endpoints, including EASI-50, and EASI change from baseline, 2-mg and 4-mg doses showed 
similar efficacy compared to placebo.  Given that the 4-mg and 2-mg doses demonstrated similar 
efficacy for a number of endpoints, it is possible that the 1-mg dose could also be beneficial, and 
thus the efficacy profile of the 1-mg dose will be evaluated.  Based on the Phase 2 study (JAHG), 
3 doses are being tested in Phase 3 adult AD studies (1, 2, and 4-mg) to cover the range of 
exposures where clinical responses could be anticipated.  
Provided that the PK lead-in confirms that exposure in older pediatric patients is comparable to 
adults, the same range of doses will be used in older pediatric patients (1, 2, and 4 mg).  If the 
PK lead-in indicates that exposures in adults and older pediatric patients are not comparable, the 
doses to be tested in JAIP will be chosen such that the expected exposure will be comparable to 
that in the adult AD studies. 
Younger pediatric population (2 to <10 years) 
In children 2 years to <10 years with AD, PBPK modelling suggests that a dose of 2-mg 
produces comparable exposure to the 4-mg dose in adults with AD.  The model-predicted AUC 
and Cmax of 2-mg in 2 to <10 year old AD patients is within the 5th and 95th percentiles of the 
AUC and Cmax of the 4-mg dose in adult patients with AD.  Therefore the maximum dose in 
children 2 to <10 years old is proposed to be 2 mg with proposed medium and low doses of 1 mg 
and 0.5 mg, respectively.  If the PK lead-in indicates that exposures in adults and children 
2 years to <10 years are not comparable, the doses to be tested in JAIP will be chosen such that 
the expected exposure will be comparable to that in the adult AD studies.  
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6. Study Population  
Prospective approvals of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, are not permitted. 
6.1. Inclusion Criteria  
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. 
Type of Patient and Disease Characteristics 
[1] Are 2 to <18 years of age and are at or above the 5th percentile of weight for 
age (e.g., ≥10.6 kg for a 2 year old) at the time of informed consent.  Full date 
of birth will be recorded except in countries where it is not allowed. 
[2] Have a diagnosis of AD at least 12 months (if ≥6 years old) and at least 
6 months (if 2 to <6 years old) 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 (Appendix 8). 
[3] Have moderate-to-severe AD, including all of the following: 
a. EASI score ≥16 at screening (Visit 1) and at Visit 2 
b. IGA score of ≥3 at screening (Visit 1) and at Visit 2 
c. ≥10% of BSA involvement at screening (Visit 1) and at Visit 2. 
[4] 
Have a documented history by a physician and/or investigator of inadequate 
response to topical corticosteroids (TCS) AND inadequate response OR history of 
intolerance to topical calcineurin inhibitors (TCNI).  Patients participating in Study 
Period 3 should be able to tolerate low- or medium-potency TCS.  
 
NOTE:  In regions where TCNI are not available or not recommended by 
treatment guidelines, only a documented history of inadequate response to 
TCS is required. 
Inadequate response is defined as failure to achieve stable long-term disease control 
(for example, IGA ≤2) based on the following criteria: 
 TCS:  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 super-potent TCS), whichever is shorter, within 6 months of 
screening. 
 
 TCNI:  after use for at least 4 weeks of treatment or for the maximum duration 
recommended by the product prescribing information, whichever is shorter. 
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 TCS and TCNI:  Patients who failed systemic therapies intended to 
treat AD within 6 months preceding screening, such as cyclosporine, 
methotrexate, azathioprine, systemic corticosteroids, or mycophenolate 
mofetil will also be considered as a surrogate for having inadequate 
response to topical therapy. 
Intolerance to TCNI is defined as:  
 a documented history of clinically significant adverse reactions that in 
the opinion of the investigator outweigh the benefits of retreatment 
(e.g., skin burning). 
NOTE:  if intolerant to TCNI, then the inadequate response criteria above 
does not need to be met for TCNI but must still be met for TCS. 
[5] Agree to discontinue use of the following excluded medications/treatments for 
at least 4 weeks prior to 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. any other systemic therapy used to treat AD or symptoms of AD 
(approved or off-label use) 
d. phototherapy, includes therapeutic phototherapy (psoralen plus 
ultraviolet-A, ultraviolet-B), excimer laser as well as self-treatment with 
tanning beds (see Section 7.7.5 regarding use as recue therapy). 
[6] Agree to discontinue use of the following excluded medications for at least 
7 days prior to Visit 2 and throughout the study unless otherwise specified 
(see Section 7.7): 
Patients participating in Study Period 2 
a. TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus) 
b. Topical PDE-4 inhibitor (crisaborole) 
Patients participating in Study Period 2 or Study Period 3 
c. Topical JAK inhibitor (e.g., tofacitinib or ruxolitinib) and/or any other 
investigative topical treatments. 
[7] Have applied emollients daily for at least 14 days prior to Visit 2 and agree to 
use emollient daily throughout the study. 
Patient Characteristics 
[8] Are male or nonpregnant, nonbreastfeeding female patients 
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Patients of childbearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex relationship 
(as part of their preferred and usual lifestyle) must agree to either remain 
abstinent or stay in a same-sex relationship without sexual relationships with 
the opposite sex. 
Total abstinence is defined as refraining from intercourse during the entirety 
of the study and for at least 4 weeks following the last dose of IP.  Periodic 
abstinence such as calendar, ovulation, symptothermal, post-ovulation 
methods and withdrawal are not acceptable methods of contraception. 
Otherwise, patients and their partners of childbearing potential must agree to use 
2 effective methods of contraception, where at least 1 form is highly effective for 
the entirety of the study and for at least 4 weeks following the last dose of IP. 
The following contraception methods are considered acceptable (the patient and 
their partner should choose 2, and 1 must be highly effective [defined as less than 
1% failure rate per year when used consistently and correctly]): 
 Highly effective birth control methods:   
o Combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:  oral, 
intravaginal, or transdermal 
o Progestogen-only hormonal contraception associated with inhibition of 
ovulation:  oral, intravaginal or implantable 
o Intrauterine device (IUD)/ intrauterine hormone-releasing system 
(IUS) 
o Vasectomized partner (with appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate). 
 Effective birth control methods:   
o Male or female condom with spermicide.  It should be noted that the 
use of male and female condoms as a double barrier method is not 
considered acceptable due to the high failure rate when these methods 
are combined. 
o Diaphragm with spermicide 
o Cervical sponge 
o Cervical cap with spermicide 
o Oral contraceptives that do not inhibit ovulation 
 
Note:  When local guidelines concerning highly effective or effective methods of 
birth control differ from the above, the local guidelines must be followed. 
Adolescent females who have started menses (even one cycle and any amount of 
spotting) are considered to be of childbearing potential. 
Females of nonchildbearing potential are not required to use birth control and they 
are defined as: 
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o Females who are infertile due to surgical sterilization (hysterectomy, 
bilateral oophorectomy, or tubal ligation), congenital anomaly such as 
mullerian agenesis, or have not started menses (and are not sexually active) 
Informed Consent 
[9] A parent or legal guardian must be able to read, understand, and give 
documented (electronic or paper signature) informed consent for a child to 
participate in this study.  In addition to informed consent given by the parent 
or legal guardian, the pediatric patient, if capable, may be required to give 
documented assent as specified by ethics board(s). 
6.2. Exclusion Criteria  
Patients will be excluded from study enrollment if any of the following criteria are met: 
Medical Conditions 
[10] 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. 
[11] Are 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 intravenous (IV) treatment for skin 
infections that may interfere with participation in the study. 
[12] Have a history of eczema herpeticum within 12 months prior to screening. 
[13] Have a history of 2 or more episodes of eczema herpeticum in the past. 
[14] Are patients who are currently experiencing a skin infection that requires 
treatment, or is currently being treated, with topical or systemic antibiotics. 
Note:  Patients may not be rescreened until at least 4 weeks after the date of 
their previous screen failure and at least 2 weeks after resolution of the 
infection. 
[15] 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). 
[16] Have been treated with the following therapies: 
a. monoclonal antibody (e.g., ustekinumab, omalizumab, dupilumab) for 
less than 5 half-lives prior to Visit 2. 
b. prior treatment with any oral JAK inhibitor (e.g., tofacitinib, ruxolitinib) 
less than 4 weeks prior to Visit 2 
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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. an intra-articular 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 during the trial. 
e. probenecid at the time of Visit 2 that cannot be discontinued for the 
duration of the study 
Medical Conditions in General 
[17] Are largely or wholly incapacitated permitting little or no self-care, such as 
being bedridden. 
[18] Have uncontrolled arterial hypertension as determined by the investigator and 
characterized by a repeated systolic or diastolic blood pressure >95th 
percentile based on age, sex and height. 
[19] Have had any major surgery within 8 weeks prior to screening or will require 
major surgery during the study that, in the opinion of the investigator in 
consultation with Lilly or its designee, would pose an unacceptable risk to the 
patient. 
[20] Are immunocompromised and, in the opinion of the investigator, at an 
unacceptable risk for participating in the study. 
[21] Have experienced any of the following within 12 weeks of screening:  VTE, 
myocardial infarction (MI), unstable ischemic heart disease, stroke, or New 
York Heart Association Stage III/IV heart failure. 
[22] Have a history of VTE or are considered at high risk of VTE as deemed by the 
investigator.  
[23] 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 IP or interfere 
with the interpretation of data. 
[24] 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. 
[25] Have a current or recent clinically serious viral, bacterial, fungal, or parasitic 
infection, including but not limited to the following: 
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Note:  A recent viral upper respiratory tract infection or uncomplicated 
urinary tract infection should not be considered clinically serious. 
a. typhoid infection within 12 weeks prior to screening. 
b. a history of herpes zoster (shingles). 
c. symptomatic herpes simplex at Visit 2. 
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). 
f. history of TB or evidence of active TB  
g. clinically serious infection or received IV antibiotics for an infection, 
within the past 4 weeks of Visit 2. 
h. any other active or recent infection within 4 weeks of Visit 2 (including 
chicken pox) that, in the opinion of the investigator, would pose an 
unacceptable risk to the patient if participating in the study. 
[26] Have received a typhoid or BCG live vaccine within 12 weeks of Visit 2 or 
have received any other live vaccine within 28 days prior to Visit 2 or intend 
to receive a live vaccine during Study Period 2 or 3.  
[27] Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug 
abuse within the 2 years prior to screening. 
[28] Have 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 on the Columbia Suicide Severity Rating Scale 
(C-SSRS) collected for patients ≥7 years old at the screening visit: 
a. Question 4 (Active Suicidal Ideation with Some Intent to Act, Without 
Specific Plan) on the “Suicidal Ideation” portion of the 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.  If this situation arises, the patient should be referred to a 
psychiatrist or appropriately trained professional as indicated. 
[29] Have donated more than a single unit of blood within 4 weeks prior to 
screening or intend to donate blood during the course of the study. 
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Prior/Concurrent Clinical Trial Experience 
[30] Are currently enrolled in any other clinical study involving an IP or any other 
type of medical research judged not to be scientifically or medically 
compatible with this study. 
[31] Have participated, within the last 30 days (3 months for studies conducted in 
the UK) in a clinical study involving an IP.   
 
If the previous IP has a long half-life (2 weeks or longer), 5 half-lives or 30 
days (whichever is longer) should have passed (3 months for studies 
conducted in the UK). 
[32] Have previously been randomized in this study or any other study 
investigating baricitinib, or who have experienced hypersensitivity to the 
active substance or to any of the excipients.   
Other Exclusions 
[33] Patient or parent/caregiver/legal guardian 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 investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted. 
[35] Are Lilly or Incyte employees or their designee. 
Diagnostic Assessments 
[36] 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. 
[37] Patients with evidence of active TB or latent TB based on medical history and 
clinical features are excluded.  In addition, if the following criteria are met, 
the patient will be excluded: 
o positive PPD test (i.e., ≥5 mm induration between approximately 48 
and 72 hours after application, regardless of vaccination history), 
and/or 
o 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 excluded.  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 excluded. 
[38] Have a positive test for HBV infection defined as: 
a. positive for hepatitis B surface antigen (HBsAg), or 
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b. positive for hepatitis B core antibody (HBcAb) and positive hepatitis B 
virus deoxyribonucleic acid (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. 
[39] Have HCV infection (positive for anti-hepatitis C antibody with confirmed 
presence of HCV ribonucleic acid [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. 
[40] Have evidence of HIV infection and/or positive HIV antibodies. 
[41] 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 
are receiving stable thyroxine replacement therapy who have TSH marginally 
outside the laboratory’s normal reference range may participate if the treating 
physician has documented that the thyroxine replacement therapy is adequate 
for the patient. 
[42] Have any of the following specific abnormalities on screening laboratory 
tests: 
a. AST or ALT ≥2x upper limit of normal (ULN) 
b. alkaline phosphatase (ALP) ≥2x ULN 
Note:  Patients may be allowed to enroll if there is no other evidence of 
liver, bone, or other abnormality but cases must be discussed and judged 
not clinically significant by Lilly Medical prior to enrollment. 
c. total bilirubin ≥1.5x ULN 
Note:  Patients may be allowed to enroll if there is no other evidence of 
liver or other abnormality but cases must be discussed and judged not 
clinically significant by Lilly Medical prior to enrollment. 
d. hemoglobin <10.0 g/dL (100.0 g/L) 
e. total white blood cell count <2500 cells/µL (<2.50x103/µL or 
<2.50 GI/L) 
f. neutropenia (absolute neutrophil count [ANC] <1200 cells/µL) 
(<1.20x103/µL or <1.20 GI/L) 
g. lymphopenia (lymphocyte count <750 cells/µL) (<0.75x103/µL or 
<0.75 GI/L) 
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h. thrombocytopenia (platelets <100,000/µL) (<100x103/µL or <100 GI/L) 
i. estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (eGFR, 
calculated using Bedside Schwartz 2009 formula). 
Note:  For cases with any of the aforementioned laboratory abnormalities 
(Exclusion Criteria [41] and [42]), 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 (patient or parent/legal guardian) must sign a new ICF, repeat all necessary screening 
procedures, and will be assigned a new identification number.   
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7. Treatments  
7.1. Treatments Administered  
This study involves a comparison of baricitinib (high, medium, and low) doses to placebo.  The 
IP will be administered by mouth once daily.  The high doses to be used in the Study Periods 3 
and 4 will be confirmed during the PK lead-in period.  Table JAIP.4 shows the proposed 
treatment regimens. 
Table JAIP.4. 
Treatment Regimens  
Regimen for Patients  
10 to <18 years old 
Open-label Investigational Product Supplied  
(Study Periods 2 and 4) 
Dose 
Baricitinib High Dose  
(4–mg QD) 
Baricitinib 4-mg tablets 
1 tablet per day 
Regimen for Patients  
2 to <10 years old 
Open-label Investigational Product Supplied  
(Study Periods 2 and 4) 
Dose 
Baricitinib High Dose  
(2–mg QD) 
Oral suspension formulationa 
1 mL per day 
Regimen for Patients  
10 to <18 years old 
Double-blind Investigational Product Supplied 
(Study Periods 3 and 4) 
Dose 
Baricitinib High Dose 
(4–mg QD) 
Baricitinib 4-mg tablets 
3 tablets per day 
Placebo to match 2-mg tablets 
Placebo to match 1-mg tablets 
Baricitinib Medium Dose  
(2–mg QD) 
Baricitinib 2-mg tablets 
3 tablets per day 
Placebo to match 4-mg tablets 
Placebo to match 1-mg tablets 
Baricitinib Low Dose  
(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 
Regimen for Patients  
2 to <10 years old 
Double-blind Investigational Product Supplied 
(Study Periods 3 and 4) 
Dose 
Baricitinib High Dose (2-mg 
QD) 
Oral suspension formulationa 
1 mL per day 
Baricitinib Medium Dose 
(1-mg QD) 
Oral suspension formulationa 
0.5 mL per day 
Baricitinib Low Dose 
(0.5-mg QD) 
Oral suspension formulationa 
0.25 mL per day 
Placebo QD 
Placebo oral suspension formulation to matcha 
1 mL per day or  
0.5 mL per day or 
0.25 mL per day 
Abbreviation:  QD = once daily. 
a The oral suspension formulation has a stability of 100 days after opening (breaking the seal).  The oral 
suspension should be dispensed as shown in the Study Schedule (Section 2).  
 
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The investigator or his/her designee is responsible for the following: 
 explaining the correct use of the investigational agent(s) to the patient and 
parent/caregiver and site personnel 
o Ensuring that patients ≥10 years old are able to swallow whole tablets  
 verifying that instructions are followed properly 
 maintaining accurate records of IP dispensing and collection 
 at the end of the study returning all unused medication to Lilly, or its designee, unless the 
Sponsor and sites have agreed that all unused medication is to be destroyed by the site, as 
allowed by local law 
7.1.1. Packaging and Labelling  
The Sponsor (or its designee) will provide the following IP: 
 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. 
 liquid suspension containing baricitinib at 2 mg/mL strength 
 liquid suspension containing placebo to match baricitinib 2 mg/mL strength 
For older patients (10 to <18 years old), packaging of the double-blind IP for each dose will 
include 3 tablets per day provided in blister packs (Study Periods 3 and 4).  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 active dose package will contain the appropriate active strength tablet, 
and corresponding placebo tablets for the other strengths, as noted in Table JAIP.4.  Open-label 
IP tablets will be provided in bottles (Study Periods 2 and 4). 
For younger patients (2 to <10 years old), baricitinib oral suspension (containing 2-mg/mL 
baricitinib) or matching placebo will be supplied as a ready-to-use oral suspension.  Baricitinib 
oral suspension will be provided in a bottle and doses will be delivered to the patient using an 
oral syringe as described in Table JAIP.4.  The Sponsor will provide an instructions for use 
(IFU) document that describes the process for administration of the oral suspension.  The 
investigator or appropriate site personnel should review the instructions for use with the patient 
and parent/caregiver to ensure understanding of the correct administration procedure for the oral 
suspension.  
Clinical study materials will be labeled according to the country’s regulatory requirements. 
7.1.2. Medical Devices  
N/A 
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7.2. Method of Treatment Assignment  
Patients participating in the PK lead-in who meet all criteria for enrollment will receive open 
label baricitinib at the high dose for their age group beginning at Visit 2. 
Patients not participating in the PK lead-in who meet all criteria for enrollment will be 
randomized in a 1:1:1:1 ratio (placebo, baricitinib low dose; baricitinib medium dose; baricitinib 
high dose) to double-blind treatment at Visit 2.  Assignment to treatment groups will be 
determined by a computer-generated random sequence using an interactive web-response system 
(IWRS).  The IWRS will be used to assign blister packs or bottles containing double-blind IP to 
each patient according to the Study Schedule (Section 2).  Site personnel will confirm that they 
have located the correct blister packs or bottles by entering a confirmation number found on the 
blister packs or bottles into the IWRS. 
Randomization will be stratified by disease severity at baseline (IGA 3 versus 4) and geographic 
region if the planned country allocation justifies.  Definitions of geographic regions and plan for 
analysis by region will described in the SAP. 
7.2.1. Selection and Timing of Doses  
The IP 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. 
At a visit where a PK sample is collected, the actual time of doses administered will be recorded 
in the patient’s electronic case report form (eCRF) according to Section 9.5.  
7.3. Blinding  
The PK-lead-in (Period 2) is open-label.  Patients who participate in the PK lead-in and transition 
to the long-term extension (Period 4) will continue on open-label IP. 
Study Period 3 is double-blind.  Patients who are responders after completion of Period 3 will 
remain on double-blind treatment during the long-term extension (Period 4).  Patients who are 
non-responders to double-blind treatment in Study Period 3 will transition to open-label 
treatment in the long-term extension (Period 4).  In addition, patients on double-blind treatment 
in Study Period 4 may be transitioned to open-label treatment if response is lost. 
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-blind 
Treatment periods.  It is expected that the need for unblinding a patient’s treatment prior to 
completion of the Double-blind 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.  Emergency unblinding for AEs may be 
performed through the IWRS.  This option may be used ONLY if the patient’s well-being 
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requires knowledge of the patient’s treatment assignment.  All calls resulting in an unblinding 
event are recorded and reported by the IWRS. 
If an investigator, site personnel performing assessments, or patient is unblinded, the patient 
must be discontinued from the study.  In cases where there are ethical reasons to have the patient 
remain in the study, the investigator must obtain specific approval from a Lilly clinical research 
physician (CRP) for the patient to continue in the study. 
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.  Where feasible 
and when timing of the emergent situation permits, the investigator should attempt to contact the 
Lilly medical monitor before unblinding a subject’s treatment assignment.  If a patient’s 
treatment assignment is unblinded, Lilly must be notified immediately that an unblinding has 
occurred, and effort should be made to keep the number of individuals at the clinical site with 
knowledge of the unblinded treatment arm to a minimum.  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.  Unblinding should only occur when 
decisions regarding patient care will be made based on whether or not the patient was on active 
drug. 
Processes to maintain blinding during the analysis conducted by the Data Monitoring Committee 
(DMC) are described in Section 10.3.8.1. 
7.4. Dosage Modification  
The baricitinib dose for an individual patient will not change during the PK lead-in period (Study 
Period 2).  However, the baricitinib dose for an age-based cohort to be randomized into Study 
Period 3 may change based on the data from the PK lead-in period.  If the data from the PK lead-
in show that the exposure for a high dose in an age group is significantly greater than expected 
and not comparable to the 4 mg dose in adults, then the dose range for that age group will be 
adjusted (i.e., the medium and low doses will be studied) for the Double-blind Treatment period 
(Study Period 3).  Patients will not be enrolled into the Double-blind Treatment period (Study 
Period 3) until the doses for an age cohort have been confirmed from the PK lead-in; therefore 
no changes in doses for an individual patient are anticipated during Study Period 3.  Patients who 
complete the PK lead-in (Study Period 2) will be eligible to enter the long-term extension 
(Period 4) on the open-label dose they received at the start of the PK lead-in period, and if the 
dose is modified for an age group after patients have already entered the long-term extension 
(Period 4), the patient will be transitioned to the modified dose.   
7.5. Preparation/Handling/Storage/Accountability  
The investigator or his/her designee is responsible for the following: 
 confirming appropriate temperature conditions have been maintained during transit for all 
study treatment received and any discrepancies are reported and resolved before use of 
the study treatment. 
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 ensuring that only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment.  All study treatments must 
be stored in a secure, environmentally controlled, and monitored (manual or automated) 
area in accordance with the labeled storage conditions with access limited to the 
investigator and authorized site staff. 
 the investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(such as receipt, reconciliation and final disposition records). 
All IP (used and partially used) will be returned to the Sponsor or destroyed at the 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 IP packaging.  
7.6. Treatment Compliance  
Patient compliance with study medication will be assessed at each visit after Visit 2 during Study 
Periods 2, 3, and 4. 
Patients treated with baricitinib or placebo will be considered to be noncompliant if they miss 
>20% of the prescribed doses during the study (unless the patient’s IP was withheld by the 
investigator for safety reasons). 
Similarly, patients will be considered to be noncompliant if they are judged by the investigator to 
have intentionally or repeatedly taken more than the prescribed amount of study medication.  
Patients found to be noncompliant with the IP should be assessed to determine the reason for 
noncompliance and educated and/or managed as deemed appropriate by the investigator to 
improve compliance. 
Patients will be counseled by study staff on the importance of taking the IP as prescribed, as 
appropriate. 
Patient 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 appropriate Concomitant Medication 
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. 
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 Daily use of emollients is required as background treatment.  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. 
 Open-label PK lead-in (Study Period 2):  Low- or mid-potency TCS (e.g., hydrocortisone 
2.5% ointment and/or triamcinolone 0.1% cream) and high- or ultra-high-potency TCS 
are only permitted as rescue therapy as described in Section 7.7.5 (Rescue Therapy).   
 Double-blind Placebo-controlled Treatment Period (Study Period 3):  Background TCS 
therapy with medium-potency and/or low-potency TCS (e.g., triamcinolone 0.1% cream 
and/or hydrocortisone 2.5% ointment) is to be used on active lesions as described in 
Section 7.7.2 (Use of Topical Corticosteroids).  
 Long-term Extension Treatment Period (Study Period 4):  Protocol-defined background 
TCS therapy (all potencies) will be allowed as concomitant treatment as described in 
Section 5.1.4. 
 TCNIs (e.g., tacrolimus and pimecrolimus) or topical PDE-4 inhibitor (i.e., crisaborole, 
where approved) are permitted in place of TCS as rescue therapy during Study Period 2 
or background therapy during Study Periods 3 and 4, 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 (Use of 
Topical Corticosteroids) and Section 7.7.5 (Rescue Therapy).   
 Phototherapy, including therapeutic phototherapy (psoralen and ultraviolet A, ultraviolet 
B, excimer laser), is permitted as rescue therapy in Period 4 at the discretion of the 
investigator (see Section 7.7.5, Rescue Therapy); however, it requires a temporary 
interruption of IP (see Section 8.1.1). 
 Bleach baths are permitted at the discretion of the investigator.  
In addition, the following therapies are permitted during the study: 
 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 vaccinations and/or emergency vaccination, such as rabies or tetanus 
vaccinations. 
It is recommended that patients using medications for sleep (including antihistamines) be on a 
stable dose for 2 weeks prior to Visit 1.  For those patients on stable dosing of medications for 
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sleep 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 on the appropriate Concomitant 
Therapy eCRF. 
Treatment with concomitant therapies for other medical conditions (not excluded per protocol) is 
permitted during the study. 
7.7.2. Use of Topical Corticosteroids  
 
Open-label PK Lead-in Period (Study Period 2) 
A washout period of 7 days is required for all TCS prior to Visit 2.  
TCS medications are not permitted during Study Period 2 except as rescue treatment (see 
Section 7.7.5 [Rescue Therapy]).  
Investigators should attempt to manage patients with emollients; however, investigators are 
allowed to rescue patients who are experiencing unacceptable or worsening symptoms of AD at 
any time.  Prior to rescue, it is recommended that increased frequency of emollient use is 
attempted to at least twice a day or more in an effort to control symptoms.  The rationale for 
rescue will be documented. 
 
Double-blind Placebo-controlled Treatment Period (Study Period 3) 
At Visit 1, patients will receive Sponsor-provided TCS (triamcinolone 0.1% cream or 
equivalent-potency TCS, and hydrocortisone 2.5% ointment or equivalent-potency TCS).  Patients 
will use the Sponsor-provided TCS medications as prescribed by the investigator (as clinically 
indicated).    
After Visit 2, medium-potency TCS (e.g., triamcinolone 0.1% cream) should continue to be 
applied to affected areas as clinically indicated until lesions are under control (clear or almost 
clear).  The medium-potency TCS should be tapered and stopped as clinically indicated (e.g., 
transition to hydrocortisone 2.5% ointment for an additional 7 days, then stop).  Low-potency TCS 
(e.g., hydrocortisone 2.5% ointment), a TCNI, or a topical PDE-4 inhibitor (e.g., crisaborole) may 
also be used to replace the medium-potency TCS on areas of thin skin (face, neck, folds, and 
genital areas) and areas with skin atrophy.  Low potency TCS and TCNIs may be used until the 
lesions are under control (clear or almost clear) and then be tapered and stopped as clinically 
indicated. 
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If lesions reappear during the course of the study, the patients should resume the application of 
medium-potency TCS (e.g., triamcinolone 0.1% cream) or low-potency TCS (e.g., hydrocortisone 
2.5% ointment), TCNI, or PDE-4 inhibitor as described above. 
Patients whose lesions persist or worsen despite the use of emollients and low- and/or 
medium-potency TCS may be considered for topical rescue with high- or ultra-high-potency TCS. 
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.  Inability to follow this guidance for use of TCS will not be considered a protocol 
violation. 
 
Long-term Extension Treatment Period (Study Period 4): 
Background TCS therapy with medium-potency and/or low-potency TCS (e.g., triamcinolone 
0.1% cream and/or hydrocortisone 2.5% ointment), TCNI, or PDE-4 inhibitor (e.g., crisaborole) 
is allowed.  For patients whose lesions persist or worsen despite the use of emollients and 
low- and/or medium-potency TCS, high- or ultra-high-potency TCS may be used as concomitant 
treatment.  
Medium-, high-, or ultra-high-potency TCS should be tapered and stopped as clinically indicated 
(e.g., transition to hydrocortisone 2.5% ointment for an additional 7 days, then stop).   
If lesions reappear during the course of the study, the patients should resume the applications of 
medium-potency TCS (e.g., triamcinolone 0.1% cream) or low-potency TCS (e.g., hydrocortisone 
2.5% ointment), high- or ultra-high-potency TCS, TCNI, or PDE-4 inhibitor as described above. 
Sponsor-provided low- and medium-potency TCS is available for dispensing through Visit 27.  At 
Visit 28 and beyond, TCS use is allowed; however, sponsor will no longer provide the TCS 
products. 
7.7.3. Use of Antihistamines  
Use of antihistamines is allowed throughout the study.  It is recommended that patients using 
antihistamines be on a stable dose for 2 weeks prior to Visit 1.  For those patients on stable 
dosing of antihistamines at entry, downward dose adjustments or discontinuation of treatment 
may occur during the study. 
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 IP will be permanently discontinued. 
 allergen immunotherapy 
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 self-treatment with tanning booth 
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 IP is required.  If the protocol guidance 
below is followed, use of these medications will not be considered a protocol violation. 
 Live vaccines may be considered during Study Period 4 if they are essential based on the 
local guideline and/or in the opinion of the investigator.  The IP should be temporarily 
interrupted for at least 12 weeks for live typhoid and BCG vaccines and for at least 28 
days for all other live vaccines including MMR or VZV booster vaccinations. 
 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 IP is required. 
 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). 
 Probenecid:  if a patient is inadvertently started on probenecid, IP should be temporarily 
interrupted and can be resumed after the patient has discontinued probenecid.  If a patient 
is not able to discontinue probenecid, then IP should be permanently discontinued. 
Prohibited Medications Requiring Permanent Discontinuation (during Study Period 4) of 
Investigational Product 
 systemic immunosuppressive/immunomodulatory substances, including, but not limited 
to, cyclosporine, methotrexate, mycophenolate mofetil, interferon-γ, azathioprine, 
biologic agents, or other JAK inhibitors (e.g., tofacitinib and ruxolitinib).  
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 Periods 2 and 3  
Choice of rescue therapy treatment (Study Period 2) 
 Triamcinolone cream 0.1% and/or hydrocortisone 2.5% ointment.  The use should be 
recorded via weight of the dispensed and returned tube and cap as indicated in the 
Schedule of Activities (Section 2).  In countries where these topical formulations are not 
available or are not considered suitable for an individual patient, an equivalent-potency 
TCS cream and/or ointment that is in line with local practices can be used.  Refer to 
Appendix 9 for guidance on potency equivalence. 
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 Investigators may also select to use TCNIs and/or crisaborole where approved, although 
it will not be provided.  If TCNIs are prescribed, use should be limited to problem areas 
only (e.g., face, neck, skin folds, genital areas, etc.). 
 On the days of study visits, topical therapy (including emollients) should not be applied 
before the patient has undergone all study procedures and clinical evaluations to allow 
adequate assessment of skin dryness. 
 Patients rescued to topical therapy will continue to take IP and use of rescue therapy will 
be documented in the eCRF. 
For patients who do not improve sufficiently with rescue topical therapy after 7 days, a higher 
potency TCS may be used (see Appendix 9), and IP may continue.  High- or ultra-high-potency 
TCS may be used once daily for up to 14 consecutive days or less 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 medium- and/or high-potency 
TCS and TCNI should be stopped, and low-potency TCS (for example, hydrocortisone 2.5% 
ointment) should be used QD for an additional 7 days, then stopped.  If lesions return, patients 
can be retreated with TCS with or without TCNIs and/or crisaborole as before, at the discretion 
of the investigator. 
Choice of rescue therapy treatment (Study Period 3) 
Patients whose lesions persist or worsen despite the use of emollients and low- and/or 
medium-potency background TCS may be considered for topical rescue with high- or 
ultra-high-potency TCS. 
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) during Study Period 3.  These patients 
will be required to discontinue IP before initiating systemic treatment.  Patients rescued to 
systemic therapies during Study Period 3 prior to the primary endpoint (Visit 8) should be 
encouraged to continue with study visits and assessments through Visit 8.  After appropriate 
discontinuation of the oral systemic treatment, patients may transition to open-label baricitinib at 
the high dose for their age group in Study Period 4.  Patient who require use of biologic 
treatments will not be allowed to enter Study Period 4. 
7.7.5.2. Rescue during Period 4  
During Period 4, patients who participated in the PK lead-in will continue on open-label 
treatment at the dose they received in the PK lead-in (high dose for age group); patients who 
were non-responders (IGA ≥3) to randomized treatment in Period 3 or who have required rescue 
with topical or systemic treatments during Study Period 3 will transition to open-label treatment 
at the high dose allowed for their age group.  Patients who were responders (IGA 0, 1, or 2) to 
randomized treatment in Period 3 without requiring rescue with topical or systemic treatments 
during Study Period 3 will continue on double-blind treatment at the same dose as initially 
randomized in Period 3.   
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During Study Period 4, for patients on double-blind treatment whose IGA worsens to 3 or 4 and 
who are unable to recapture an IGA response of 0, 1, or 2, despite the use of emollients and TCS 
(as described in Section 7.7.2), the patient may be transitioned at the discretion of the 
investigator to open-label baricitinib at the high dose for their age group.  
After the first year of the extension treatment period, treatment and transition to open-label 
baricitinib will continue as described above; however, patients will be allowed to voluntarily 
interrupt baricitinib treatment (drug holiday) as described in Section 5.1.4, provided they 
continue to complete all other study visit procedures per protocol.  The IP may be resumed at the 
same dose after a voluntary interruption if symptoms worsen. 
Patients may be rescued with phototherapy at the discretion of the investigator during 
Study Period 4.  Patients rescued with phototherapy will remain in the study and be required to 
temporarily interrupt use of IP until completion of the phototherapy (see Section 8.1.1 for 
Temporary Interruption of Investigational Product). 
Patients who require rescue with systemic therapies (conventional systemics or biologics) during 
Period 4 will be considered to be nonresponders and will be discontinued from the study.  
7.8. Treatment after the End of the Study  
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 Discontinuation from Study Treatment  
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 IP.  For example, IP 
should be temporarily interrupted if the patient experiences a cardiovascular adverse event 
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 JAIP.5.   
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table JAIP.5, 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 is at the discretion of the investigator.  Investigational product that was 
temporarily interrupted because of an AE or abnormal laboratory value not specifically covered 
in Table JAIP.5 may be restarted at the discretion of the investigator. 
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Table JAIP.5. 
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/µL 
(<2.00x103/µL or <2.00 GI/L) 
WBC count 2500 cells/µL 
(≥2.50x103/µL or ≥2.50 GI/L) 
ANC <1000 cells/L 
(<1.00x103/µL or <1.00 GI/L) 
ANC ≥1200 cells/µL 
(≥1.20x103/µL or ≥1.20 GI/L) 
Lymphocyte count <500 cells/µL 
(<0.50x103/µL or <0.50 GI/L) 
Lymphocyte count 750 cells/µL 
(≥0.75x103/µL or ≥0.75 GI/L) 
Platelet count <75,000/µL 
(<75x103/µL or <75 GI/L) 
Platelet count 100,000/µL 
(≥100x103/µL or ≥100 GI/L) 
eGFR <50 mL/min/1.73 m2 (from serum creatinine)  
eGFR 60 mL/min/1.73 m2 
ALT or AST >5x ULN 
ALT and AST return to <2x 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 (shingles or chicken pox) 
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 ruling out event of VTE 
Abbreviations:  ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; GI = billion; 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 or permanent discontinuation criteria are met, then IP may be resumed.  
 
Although temporary interruption of IP is not a requirement at times of increased potential risk of 
VTE (e.g., surgery, significant air travel, or other situations involving prolonged 
immobilization), following appropriate VTE prophylaxis guidelines is recommended to help 
manage the VTE risk under these circumstances.  
If rescue with phototherapy is required during Study Period 4, then the IP must be temporarily 
interrupted until the phototherapy treatments have been completed (see Section 7.7.5, Rescue 
Therapy). 
During the long-term extension the patient will be allowed to receive live vaccines with 
appropriate interruption of baricitinib treatment prior to and after the live vaccine (see 
Section 7.7.4). 
Lastly, IP 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  
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 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 IP, it is recommended that the patient be assessed by a 
psychiatrist or appropriately trained professional to assist in deciding whether the subject should 
remain on IP and ultimately continue participation in the study.  A patient does not necessarily 
have to have IP interrupted if they have self-injurious behavior that would be classified as non-
suicidal self-injurious behavior.   
8.1.2. Permanent Discontinuation from Study Treatment  
Investigational product should be permanently discontinued if the patient or the patient’s 
designee (parent/legal guardian/caregiver) requests to discontinue IP. 
Discontinuation due to a hepatic event or liver test abnormality.   
Patients who are discontinued from IP due to a hepatic event or liver test abnormality should 
have additional hepatic safety data collected via case report form (CRF) or other designated data 
transmission methods. 
Discontinuation of the IP for abnormal liver tests should be considered by the investigator when 
a patient meets one of the following conditions after consultation with the Lilly designated 
medical monitor: 
 ALT or AST >8× ULN 
 ALT or AST >5× ULN for more than 2 weeks 
 ALT or AST >3× ULN and total bilirubin level (TBL) >2× ULN or international 
normalized ratio (INR) >1.5  
 ALT or AST >3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, and/or rash 
 ALP >3× ULN (unless allowed after discussion with Sponsor) 
 ALP >2.5× ULN and TBL >2× ULN 
 ALP >2.5× ULN with the appearance of fatigue, nausea, vomiting, right quadrant pain or 
tenderness, fever, and/or rash 
Investigational product should be permanently discontinued if any of the following laboratory 
abnormalities are observed: 
 white blood cell count <1000 cells/µL (1.00x103/µL or 1.00 GI/L) 
 ANC <500 cells/µL (0.50x103/µL or 0.50 GI/L) 
 lymphocyte count <200 cells/µL (0.20x103/µL or 0.20 GI/L) 
 hemoglobin <6.5 g/dL (<65.0 g/L). 
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NOTE:  Temporary interruption rules (see Section 8.1.1) must be followed where 
applicable.  For laboratory values that meet permanent discontinuation thresholds, IP 
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 JAIP.5) following the resolution of the intercurrent 
illness or other identified factor may the investigator restart IP, after consultation with 
the Lilly-designated medical monitor. 
In addition, patients will be discontinued from IP in the following circumstances: 
 pregnancy 
 malignancy  
 hepatitis B virus DNA is detected with a value above the limit of quantitation or 2 
sequential tests return a value of below the limit of quantitation (see Section 9.4.8). 
 develop a VTE event 
If a patient who is participating in the Double-blind Treatment period (Study Period 3) 
discontinues IP 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 IP 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 CRP agree it is medically appropriate to 
continue, the investigator must obtain documented approval from the Sponsor CRP to allow the 
inadvertently enrolled patient to continue in the study with or without treatment with IP.  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. 
In some instances, it will be clear that the inadvertently enrolled patient needs to be withdrawn 
from the study drug.  This is the case for important protocol deviations, where it is clear that the 
protocol deviation(s) may significantly impact the completeness, accuracy, and/or reliability of 
the study data or may significantly affect a subject’s rights, safety, or well-being (ICH 2012).  In 
other instances, where the protocol deviation is considered non-important since it will not 
significantly impact patient safety or interpretation of the study data, the Investigator and the 
Sponsor may agree it is medically appropriate to allow the patient to continue in the study with 
appropriate documentation of the rationale.  Preplanned per-protocol analyses will be described 
in the statistical analysis plan for the study and will include analyses of key efficacy endpoints 
with and without data from patients with protocol deviations.  
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8.2. Discontinuation from the Study  
Patients/parents/caregivers may choose to withdraw from the study for any reason at any time, 
and the reason for early withdrawal will be documented. 
Patients will be discontinued in the following circumstances:  
 enrollment in any other clinical study involving an IP 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) 
 study termination may occur in a specific country or region when baricitinib is approved 
for the treatment of AD and becomes reimbursed or commercially available in that 
country or region, or a negative regulatory opinion is received in that country or region 
 investigator decision 
o the investigator decides that the patient should be discontinued from the study 
o if the patient, for any reason, requires treatment with another 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. 
 
Patients discontinuing from the study prematurely for any reason should complete AE and other 
safety follow-up per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol. 
8.3. Lost to Follow-Up  
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site. 
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9. Study Assessments and Procedures  
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing). 
Appendix 2 lists the laboratory tests that will be performed for this study. 
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards. 
9.1. Efficacy Assessments  
Please refer to the Schedule of Activities (Section 2) and Appendix 6 for details on frequency of 
collection, method of data collection, method of administration, and age range of administration 
for all efficacy and health outcomes and quality-of-life measures. 
9.1.1. Primary Efficacy Assessments  
Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD):  The IGA 
used in this study is the vIGA-AD (referred to as the IGA throughout the protocol) and 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 skin) to 4 (severe disease) (information available at 
WWW.eczemacouncil.org).  The score is based on an overall assessment of the degree of 
erythema, papulation/induration, oozing/crusting, and lichenification. 
The IGA is a commonly used scale in clinical trials in adult and pediatric patients (Langely et al. 
2015; Futamura et al. 2016).  
9.1.2. Secondary Efficacy Assessments  
9.1.2.1. Eczema Area and Severity Index scores  
The investigator-rated 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. 
The EASI is a validated scale in patients down to 2 months of age (Barbier et al. 2004). 
9.1.2.2. SCORing Atopic Dermatitis  
The SCORing Atopic Dermatitis (SCORAD) index is an investigator-rated assessment that 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 (via patient-rated visual analog scale).  These 3 aspects:  extent of disease, 
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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. Immunological Measurements  
Patients will be immunized with appropriate vaccinations as part of or in the course of their usual 
care according to the local requirement throughout the study period.  When the patients become 
eligible for a TDaP and/or a pneumococcal conjugate vaccine during the study, they are 
immunized with the vaccines and their antibody titers to the antigens will be evaluated pre-
immunization and at 4 and 12 weeks post-immunization.  A primary immune response will be 
assessed in patients who have never received TDaP or pneumococcal conjugate vaccines 
previously and secondary/booster responses will be assessed if the patients have previously 
received the vaccines. 
9.1.4. 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. 
9.1.4.1. Patient-Oriented Eczema Measure  
The Patient-Oriented Eczema Measure (POEM) is a simple, 7-item, patient-administered scale 
that assesses disease severity in children and adults.  Patients respond to questions about the 
frequency of 7 symptoms (itching, sleep disturbance, bleeding, weeping/oozing, cracking, 
flaking, and dryness/roughness) over the last week.  Response categories include “No days,” “1-
2 days,” “3-4 days,” “5-6 days,” and “Every day” with corresponding scores of 0, 1, 2, 3, and 4, 
respectively.  Scores range from 0 to 28 with higher total scores indicating greater disease 
severity (Charman et al. 2004). 
The POEM is a validated scale in patients down to 1 year of age (Charman et al. 2004). 
9.1.4.2. 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.”  
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). 
9.1.4.3. Skin Pain Numeric Rating Scale  
Skin Pain NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 
representing “no pain” and 10 representing “worst pain imaginable.”  Overall severity of a 
patient’s skin pain is indicated by selecting the number that best describes the worst level of skin 
pain in the past 24 hours. 
9.1.4.4. 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.  Patient’s rate their difficulty falling asleep 
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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.  
9.1.4.5. Patient Global Impression of Severity  
The Patient Global Impression of Severity–Atopic Dermatitis (PGI-S-AD) is a single-item 
question asking the patient how they would rate their overall AD symptoms over the past 
24 hours.  The 5 categories of responses range from “no symptoms” to “severe.” 
9.1.4.6. PROMIS Depression Short Form  
Patient-Reported Outcomes Measurement Information System (PROMIS) is a set of person-
centered measures that evaluates and monitors physical, mental, and social health in adults and 
children (information available at WWW.healthmeasures.net; PROMIS - Depression).  It can be 
used with the general population and with individuals living with chronic conditions.  The 
PROMIS Depression item bank assesses self-reported negative mood (sadness, guilt), views on 
self (self-criticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as 
well as decreased positive affect and engagement (loss of interest, meaning, and purpose).  The 
PROMIS Depression Short Form (8a v2.0 and 6a v2.0) is available in a pediatric self-report 
(ages 8 to <18 years) and for parents/caregivers serving as proxy reporters for their children 
(youth ages ≥5 years).  Children aged <5 years will not complete this assessment.  Both pediatric 
self-report and proxy-report versions assess depression “in the past seven days.”  Response 
options range from 1 = Never; 2 = Rarely; 3 = Sometimes; 4 = Often; to 5 = Almost always.  
Total raw scores are converted to T-Scores with higher scores representing greater depression.  
9.1.4.7. PROMIS Anxiety Short Form  
Patient-Reported Outcomes Measurement Information System (PROMIS) is a set of person-
centered measures that evaluates and monitors physical, mental, and social health in adults and 
children (information available at WWW.healthmeasures.net; PROMIS - Anxiety).  It can be 
used with the general population and with individuals living with chronic conditions.  The 
PROMIS Anxiety item bank assesses self-reported fear (fearfulness, panic), anxious misery 
(worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related 
to arousal (racing heart, dizziness).  The PROMIS Anxiety Short Form (8 questions, 8a v2.0) is 
available in a pediatric self-report (ages 8 to <18 years) and for parents/caregivers serving as 
proxy reporters for their children (youth ages ≥5years).  Children aged <5 years will not 
complete this assessment.  Both pediatric self-report and proxy-report versions assess anxiety “in 
the past seven days.”  Response options range from 1= Never; 2 = Rarely; 3 = Sometimes;  
4 = Often; to 5 = Almost always.  Total raw scores are converted to T-Scores with higher scores 
representing greater anxiety.  
9.1.4.8. Infants’ Dermatitis Quality of Life Index  
The Infant’s Dermatitis Quality of Life Index (IDQOL) is a simple, caregiver-administered, 
11-question, validated, quality-of-life questionnaire that is designed for use in pediatric patients 
<4 years old with AD (Lewis-Jones et al. 2001; Basra et al. 2013).  It is completed by the child’s 
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parent or regular caregiver.  It covers 2 domains including Dermatitis Severity and Life Quality 
Index.  The recall period is over the “last week.”  Response categories for the Dermatitis Severity 
domain include “None,” “Fairly good,” “Average,” “Severe,” and “Extremely severe” with 
corresponding scores of 0, 1, 2, 3, and 4, respectively.  The Life Quality Index domain response 
categories vary for individual questions; however, each question has 4 response options with 
corresponding scores ranging from 0-3.  Total scores of the Life Quality Index range from 0-30 
with higher scores indicating greater impairment of quality of life.  The Dermatitis Severity is 
scored separately and can be correlated with the IDQOL.  An IDQOL total score of 0 to 1 is 
considered as having no effect on a child’s life. 
9.1.4.9. Children’s Dermatology Life Quality Index  
The Children’s Dermatology Life Quality Index (CDLQI) is a simple, patient-administered, 
10-question, validated, quality-of-life questionnaire that is designed for use in children ≥4 years 
old that covers 6 domains including symptoms and feelings, leisure, school or holidays, personal 
relationships, sleep, and treatment (Lewis-Jones and Finlay 1995).  The recall period is over the 
“last week.”  Response categories include “not at all,” “only a little,” “quite a lot,” and “very 
much,” with corresponding scores of 0, 1, 2, and 3, respectively, with unanswered (“not 
relevant”) responses scored as 0 and “Prevented School” scored as 3.  Scores range from 0 to 30 
with higher scores indicating greater impairment of quality of life.  A CDLQI total score of 0 to 
1 is considered as having no effect on a child’s life (Waters et al. 2010). 
9.1.4.10. Dermatitis Family Impact Questionnaire  
The Dermatitis Family Impact (DFI) questionnaire is a simple, caregiver-administered, 10-
question, validated, quality-of-life questionnaire that is designed to assess the impact of AD on 
the quality of life of the parents and family members of children with AD (Lawson et al. 1998; 
Dodington et al. 2013).  The recall period is over the “last week.”  Response options include 
“Not at all,” “A little,” “A lot,” and “Very much,” with corresponding scores of 0, 1, 2, and 3, 
respectively.  Scores range from 0 to 30 with higher scores indicating greater impairment of 
quality of life.  
9.1.4.11. European Quality of Life–5 Dimensions–Youth  
The European Quality of Life-5 Dimensions-Youth version (EQ-5D-Y) is a widely used, generic 
questionnaire that assesses health status “today” (The EuroQol Group 2014).  The EQ-5D-Y is 
self-completed for pediatric patients ≥8 years old and is completed by parents/caregivers (proxy) 
for children 4 to <8 years old.  This assessment will not be completed for children <4 years old 
per developer recommendation.  The questionnaire consists of 2 parts:  the first part assesses 
5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that 
have 3 possible levels of response (no problems, some problems, or a lot of problems).  This part 
of the EQ-5D-Y can be used to generate a health state index score, which is often used to 
compute QALY for utilization in health economic analyses.  The health state index score is 
calculated based on the responses to the 3 dimensions, providing a single value on a scale from 
less than 0 (where zero is a health state equivalent to death; negative values are valued as worse 
than dead) to 1 (perfect health), with higher scores indicating better health utility. 
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The second part of the questionnaire consists of a visual analog scale on which the patient rates 
their perceived health state from 0 (“the worst health you can imagine”) to 100 (“the best health 
you can imagine”).  Published studies by EuroQol Group members showed preliminary evidence 
of the instrument’s feasibility, reliability, and validity (Ravens-Sieberer et al. 2010).   
9.1.4.12. Work Productivity and Activity Impairment Questionnaire:  Atopic 
Dermatitis - Caregiver  
The Work Productivity and Activity Impairment Questionnaire:  Atopic Dermatitis Caregiver 
(WPAI-AD-CG) assesses the effect of a child’s AD on the parent/caregiver’s work productivity 
during the past 7 days.  The WPAI-AD-CG 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, 
1996), with higher scores indicating greater impairment and less productivity. 
9.1.4.13. Parent-Reported Itch Severity Measure  
The Parent-Reported Itch Severity Measure (PRISM) is a single-item, parent/caregiver-
administered scale that reports the overall severity of their child’s itching.  Parent/Caregiver’s 
report the overall severity of their child’s itching based on observed actions of the child in the 
past 24 hours.  Response options range include “No Itch,” “Mild,” “Moderate,” “Severe,” and 
“Very Severe.”  The PRISM will be completed for patients <10 years old by the 
parent/caregiver. 
9.1.4.14. Additional Assessments (TCS Use, Missed School Days)  
Topical corticosteroids use will be collected using a daily diary.  This is a single question used to 
record if a patient has applied a TCS to the skin in the last 24 hours.  Either the patient or 
parent/caregiver can provide the response. 
The number of missed school days for school age children will be reported via daily diary by the 
parent/caregiver or patient. 
9.1.5. Product Acceptability and Palatability Assessments  
The assessment of acceptability and palatability of the baricitinib formulations (tablet and oral 
suspension) will only be collected for patients participating in the Open-label PK Lead-in period 
(Study Period 2).  
The patient and/or parent/caregiver will be asked to provide responses to questions designed to 
assess the acceptability and palatability of the formulations, either tablet or oral suspension.  The 
questionnaire for tablet acceptability will assess the patient’s ability to swallow the tablet.  The 
questionnaire for suspension acceptability and palatability will assess the patient’s experience 
relating to the taste and smell of the suspension and ease of administering and taking the 
suspension (Davies and Tuleu 2008; Kozarewicz 2014). 
The appropriate questionnaire will be administered at baseline (Visit 2, after dosing) and Visit 4 
(after approximately 2 weeks of use).  The questionnaire will be responded to by 
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parents/caregivers (proxy) for children aged 2 to <10 years (suspension formulation).  For 
children aged 10 years and older, the questionnaire will be self-completed (tablets). 
9.1.6. Appropriateness of Assessments  
All assessments utilized in this study are standard, widely used, and generally recognized as 
reliable, accurate, and relevant except the Skin Pain NRS, ADSS, PGI-S-AD, PRISM, missed 
school days, and acceptability/palatability 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 IP or the study, 
or that caused the patient to discontinue the IP before completing the study.  The patient should 
be followed until the event resolves or stabilizes with appropriate diagnostic evaluation; for 
events that are not anticipated to resolve or stabilize, the patient should be followed until the 
treating physician (in consultation with the Sponsor) determines that appropriate follow-up has 
been completed.  The frequency of follow-up evaluations of the AE is left to the discretion of the 
investigator. 
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect. 
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs.  Investigators should record their assessment of the 
potential relatedness of each AE to protocol procedure and IP, via eCRF.  
Investigators should record the following via eCRF for each AE:  date of onset, date of 
termination, severity, and their assessment of the potential relatedness of each AE to IP. 
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment or pathologies.  A “reasonable possibility” means that there is a 
cause and effect relationship between the IP, 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. 
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If a patient’s IP is discontinued as a result of an AE, study site personnel must report this to Lilly 
or its designee via eCRF, clarifying if possible, the circumstances leading to any dosage 
modifications, or discontinuations of treatment.  
9.2.1. Serious Adverse Events  
An SAE is any AE from this study that results in one of the following outcomes: 
 death 
 initial or prolonged inpatient hospitalization 
 a life-threatening experience (that is, immediate risk of dying) 
 persistent or significant disability/incapacity 
 congenital anomaly/birth defect 
 important medical events that may not be immediately life-threatening or result in death 
or hospitalization but may jeopardize the patient or may require intervention to prevent 
one of the other outcomes listed in the definition above.  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 IP.  However, if an SAE occurs after signing the ICF, but prior to receiving IP, the SAE 
should be reported to the Sponsor as per SAE reporting requirements and timelines (see 
Section 9.2) if it is considered reasonably possibly related to study procedure. 
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via initiation of SAE eCRF.  Once the SAE eCRF form is initiated, an 
email is automatically triggered to the Sponsor’s global patient safety department.  Investigators 
can contact the Sponsor via telephone at any time using the qualified medical personnel or Lilly 
affiliate medical contact details which are provided in the site study file.  If alerts are issued via 
telephone, they are to be immediately followed with official notification via completion of the 
SAE eCRF.  If the eCRF is unavailable (for example, for system maintenance) for a period of 
time that would compromise the sites’ ability to report an event within 24 hours of awareness, a 
paper version of the form should be downloaded from the Investigator Space portal, completed 
by the investigator, and submitted via fax to the Sponsor’s global patient safety department.  This 
form includes a fax cover page that is pre-populated with the appropriate fax number.  Serious 
adverse events submitted via the paper method are entered into the eCRF once the database is 
available.  The 24-hour notification requirement refers to the initial SAE information and all 
follow-up SAE information.  Patients with a serious hepatic adverse event should have additional 
data collected using the eCRF. 
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Pregnancy (during maternal or paternal exposure to IP) does not meet the definition of an AE.  
However, to fulfill regulatory requirements any pregnancy should be reported following the SAE 
process to collect data on the outcome for both mother and fetus. 
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient disposition CRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/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 IP or procedure.  United States 21 CFR 
312.32 and European Union Clinical Trial Directive 2001/20/EC and the associated detailed 
guidances or national regulatory requirements in participating countries require the reporting of 
SUSARs.  Lilly has procedures that will be followed for the 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 tuberculosis [TB], herpes zoster, or opportunistic infections) 
 malignancies (except for successfully treated basal or squamous cell skin carcinoma) 
 hepatic events (see Section 9.4.9.1) 
 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 IPs 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 IP so that the situation can be assessed. 
9.3. Treatment of Overdose  
Baricitinib single doses up to 40-mg and multiple doses of up to 20-mg daily for 10 days have 
been administered in clinical studies without dose-limiting toxicity.  Pharmacokinetic data of a 
single dose of 40-mg in healthy volunteers indicate that >90% of the administered dose is 
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expected to be eliminated within 24 hours.  In case of an overdose, the patient should be 
monitored for signs and symptoms of adverse reactions.  Patients who develop adverse reactions 
should receive appropriate treatment. 
9.4. Safety  
Any clinically significant findings from electrocardiogram (ECG) testing, physical examination, 
vital signs measurements, or laboratory measurements that result in a diagnosis and that occur 
after the patient receives the first dose of study treatment should be reported to Lilly or its 
designee as an AE via eCRF. 
9.4.1. Electrocardiograms  
A single 12-lead standard ECG will be obtained locally at Visit 1 and read by a qualified 
physician (the investigator or qualified designee) at the site to determine whether the patient 
meets entry criteria.  Electrocardiograms may be obtained at additional times, when deemed 
clinically necessary.  
9.4.2. Vital Signs  
For each patient, vital signs measurements should be conducted according to the Schedule of 
Activities (Section 2).   
Blood pressure readings will be collected using the appropriate size pediatric blood pressure 
cuffs.  
Any clinically significant findings from vital signs measurement 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 CRF/electronic data entry / designated data transmission methods. 
9.4.3. Laboratory Tests  
For each patient, laboratory tests detailed in (Appendix 2) should be conducted according to the 
Schedule of Activities (Section 2).  Flexibility in blood sample collection is allowed where blood 
sample volume restrictions may apply; refer to protocol Appendix 13. 
Use of local anesthetics (e.g., EMLA cream) consistent with local prescribing information are 
permitted during the study visit to ease discomfort associated with venipunctures.  Home visits to 
collect blood and urine samples may be allowed upon written approval from the sponsor and if 
consistent with local regulations. 
Alkaline phosphatase laboratory results may be out of the normal range in pediatric patients 
because of normal bone growth processes, and collection of a blood sample for bone alkaline 
phosphatase may be requested by the Sponsor as a reflex test if the alkaline phosphatase result is 
high. 
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.   
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Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of IP should be reported to Lilly or its designee as an AE 
via CRF/electronic data entry / designated data transmission methods. 
Fasting Laboratory Tests: 
Recommended fasting times by age and weight are as follows: 
 Adolescents ≥12 years:  fast for 12 hours prior to laboratory test 
 Children 8 to <12 years and weighing >50 kg:  fast for 12 hours prior to laboratory test 
 Children 8 to <12 years and weighing ≤50 kg:  fast for 8 hours prior to laboratory test 
 Children <8 years and weighing 25 to ≤50 kg:  fast for 8 hours prior to laboratory test 
 Children <8 years and weighing 10 to ≤25 kg:  fast for 6 hours prior to laboratory test 
 Children <8 years and weighing <10 kg:  fast for 4 hours prior to laboratory test 
Urinalysis: 
If an urinalysis sample is unable to be collected in younger children, particularly those who have 
not been toilet trained, this will not be considered to be a protocol violation provided that the site 
maintains appropriate documentation of why the sample is missing. 
 
9.4.4. Physical Exam  
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. 
9.4.4.1. Tanner Stage Scale  
The Tanner Stage Scales are a series of line drawings that are designed to assess sexual maturity 
of the patient, and will be included as a baseline assessment.  The line drawings are intended for 
patient self-assessment; however, this assessment may be also conducted by an appropriate 
health care professional if the patient and legal guardian agree (Marshall and Tanner 1969, 1970; 
Tanner and Davies 1985; Chavarro et al. 2017).  Assessment by the health care professional will 
not be completed if the patient and parent do not provide appropriate consent and assent.  The 
self-assessment will only be collected if the appropriate translation of the scale is available for 
use at the time of the baseline assessment. 
9.4.5. Columbia Suicide Severity Rating Scale  
The Columbia Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and 
frequency of suicidal ideation and/or behavior during the assessment period.  The C-SSRS will 
only be collected in patients ≥7 years old.  A children’s version of the C-SSRS will be completed 
for patients 7 to <12 years old, and an adolescent/adult version of the C-SSRS will be completed 
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for patients 12 to <18 years old.  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 qualified site personnel.  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. 
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. Tuberculosis Testing  
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.  
9.4.8. Hepatitis B Virus DNA Monitoring  
Patients who are HBcAb positive and HBV DNA negative (undetectable) at Visit 1 will require 
measurement of HBV DNA per the Schedule of Activities, 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 
IP (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. 
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In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, only members of the data monitoring committee (an advisory group for this 
study formed to protect the integrity of data; refer to Interim Analyses section [Section 10.3.8]) 
can conduct additional analyses of the safety data. 
The Lilly CRP will monitor safety data throughout the course of the study.  Lilly will review 
SAEs within time frames mandated by company procedures.  The Lilly clinical research 
physician will, as is appropriate, consult with the functionally independent Global Patient Safety 
therapeutic area physician or clinical scientist and periodically review trends in safety data and 
laboratory analytes.  Any concerning trends in frequency or severity noted by an investigator 
and/or Lilly (or designee) may require further evaluation. 
All deaths and SAE reports will be reviewed 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 IP, 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 and arterial 
thrombotic events, and noncardiovascular deaths will be identified by the investigative 
site or through medical review and will be sent to a blinded Clinical Event Committee for 
adjudication at regular intervals. 
9.4.9.1. Hepatic Safety Monitoring  
If a study patient experiences elevated ALT ≥3X upper limit of normal (ULN), alkaline 
phosphatase (ALP) ≥2X ULN (for patients with baseline <2x ULN), or elevated TBL ≥2X 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.  
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Hepatic Safety Data Collection 
Additional safety data should be collected via the case report form (CRF) or other designated 
data transmission methods if 1 or more of the following conditions occur:  
 elevation of serum ALT to ≥5X ULN on 2 or more consecutive blood tests 
 elevated serum TBL to ≥2X ULN (except for cases of known Gilbert’s syndrome)  
 elevation of serum ALP to ≥2X ULN on 2 or more consecutive blood tests (for patients 
with baseline <2x ULN) 
 patient discontinued from treatment due to a hepatic event or abnormality of liver tests 
 hepatic event considered to be a SAE 
9.4.9.2. Venous Thromboembolic Event Assessment  
If a patient develops the clinical features of a deep vein thrombosis or pulmonary embolism, 
appropriate local laboratory tests and imaging are recommended, as necessary, for diagnosis of 
the event.  For confirmed cases, additional laboratory testing should be performed as outlined in 
Appendix 5.  All suspected VTE events will be independently adjudicated by an external blinded 
Clinical Event Committee. 
9.4.9.3. Growth Monitoring  
Height and weight, left hand x-rays, knee x-rays, hormone levels, and occipital frontal 
circumference will be collected as described below and according to the Schedule of Activities 
(Section 2) to allow for the identification of potential effects on growth and development: 
 Height measurements will be made using a stadiometer.  Height measurements must be 
recorded to 1 decimal place without rounding.   
 Weight measurements must be recorded to 1 decimal place without rounding.  
 Instruments used for measuring height and weight should be appropriately and regularly 
calibrated. 
 All measurements of height and weight should be made without shoes and after the 
removal of any heavy personal items (that is, large jewelry, wallets, coats, etc.).  
 Height and weight changes in pediatric patients (both at an individual and group level) 
will be reviewed by the DMC external to Lilly. 
 Left hand x-rays will be collected to assess effects on bone age. 
o Ongoing patients will have hand x-rays completed approximately every 6 months 
per the Schedule of Activities (Section 2) after approval of this protocol 
amendment and completion of the consent form.  A central vendor will be used 
for reading of the x-ray images. 
 Knee x-rays will be collected to monitor bone growth. 
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o An x-ray of the knee (anteroposterior) will be collected approximately every 
6 months as shown in the Schedule of Activities (Section 2).  A central vendor 
will be used for reading of the x-ray images. 
o Ongoing patients will have a knee x-ray at the next scheduled visit after approval 
of this protocol amendment and completion of the consent form.  Subsequent 
knee x-rays will be collected per the Schedule of Activities (Section 2), unless the 
subsequent visit is within 3 months of the first knee x-ray, in which case the knee 
x-ray can be skipped at this timepoint to avoid unnecessary radiation exposure. 
o If a local addendum is in place that specifies another mode of imaging (e.g., 
magnetic resonance imaging [MRI] instead of x-ray), the local addendum should 
be followed.  Otherwise, the current protocol amendment should be followed with 
regard to knee x-rays.  
 Any symptomatic areas of bones/joints will be assessed and investigated as appropriate 
by study investigators.  Any diagnoses made based on symptomatic areas of bones/joints 
or imaging data will be reported as appropriate (e.g., recorded on eCRF). 
 Biomarkers that will be collected to provide information on bone health include:  ALP 
and calcium (collected as part of the clinical chemistry panel). 
 Insulin-like growth factor (IGF)-1, the principal mediator of growth hormone, and IGF-
binding protein (IGF-BP)-3, the principal carrier protein for IGF-1, will be collected for 
the assessment of growth-related disorders. 
 Gonadal hormones (estradiol for females or testosterone for males) will be collected for 
the assessment of pubertal development in patients 8 to <18 years of age.   
9.5. Pharmacokinetics  
9.5.1. Open-label PK Lead-in (Study Period 2)  
Blood samples will be collected during the Open-label PK Lead-in period using a commercially 
available microsampling device (see Schedule of Activities in Section 2).  These blood samples 
will be used to determine the concentrations of baricitinib using a validated bioanalytical 
method.  The timing will be as follows: 
 At Visit 2 (Week 0/Day 1), patients will take their first dose of IP in the clinic, and PK 
samples will be collected 15 minutes and 1 hour postdose.   
 On Day 2 and thereafter:  patients will take their IP once daily at home.  Patients should 
be instructed to take their dose at approximately the same time each day. 
 On Day 4, patients will take their IP at home, and PK samples will be collected at 2 hours 
and 4 hours postdose.  If PK samples are not collected on Day 4, they may be collected 
on the following days up to and including the date of Visit 3 (Week 1). 
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 On Day 11, a PK sample will be collected BEFORE the IP is taken.  Immediately after 
the PK sample is collected, the patient will take the IP, and PK samples will be collected 
at 30 minutes and 6 hours postdose.  If PK samples are not collected on Day 11, they may 
be collected on the following days up to and including the date of Visit 4 (Week 2).  All 
PK samples must be completed before the patient leaves the clinical site at Visit 4. 
One patient in the older age group may be selected to provide 1 venous blood sample to assess 
concordance between venous blood samples and microsamples. During Study Period 2, the 
actual date and 24-hour clock time of the PK sample collection, and the date and time of the last 
2 doses of IP will be recorded.  For samples drawn on Day 4 and 11, the 2 previous doses should 
be the dose given on the day of the PK sample collection and the dose given the previous day. 
9.5.2. Double-blind Treatment Period (Study Period 3)  
A venous blood sample will be drawn at the times indicated in the Schedule of Activities 
(Section 2) (Weeks 0 [first dose, 2 samples], 4, 8, 12, and 16).  These blood samples will be used 
to determine the plasma concentrations of baricitinib using a validated bioanalytical method.  
The timing will be as follows: 
 At Visit 2 (Week 0), patients will take their IP in the clinic, and PK samples will be 
drawn 15 minutes and 1 hour postdose.  NOTE:  At Visit 2, all other laboratory samples 
(i.e., all non-PK samples) will be obtained prior to the first dose of IP in order to ensure 
accurate baseline data are collected.  
 At Visit 5 (Week 4), patients will be asked to take their IP at home prior to visiting the 
clinic.  The clinic visit should be scheduled so that the blood sample collected during this 
visit is drawn 2 to 4 hours after the dose is taken at home. 
 For Visit 6 (Week 8) and Visit 7 (Week 12) patients will be asked to not take their IP 
before visiting the clinic, and a blood sample will be collected at any time predose on the 
day of the clinic visits.  If the patient has taken the oral dose prior to the visit, the sample 
may be drawn anytime postdose, and the inability to collect a predose sample will not be 
considered a protocol violation. 
 At Visit 8 (Week 16), patients will be asked to take their IP at home prior to visiting the 
clinic.  The clinic visit should be scheduled so that the blood sample collected during this 
visit is drawn 4 to 6 hours after the oral dose is taken at home. 
 For the ETV, a sample may be drawn anytime if the last dose of IP was taken within the 
last 48 hours. 
For visits where PK samples will be collected, the actual date and 24-hour clock time of sample 
collection, and the date and time of the last 2 doses prior to the sample being drawn, should be 
recorded.  At Visit 5 (Week 4) and Visit 8 (Week 16), these 2 doses should be the dose given the 
morning of the day of sample collection and the dose given the previous day.  At Visit 6 
(Week 8) and Visit 7 (Week 12), the 2 previous doses should be the dose taken yesterday and the 
dose taken the day before that. 
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This sampling schedule should be followed as closely as possible; however, failure to take PK 
samples at these specified times will not be considered a protocol violation.  If the patient fails to 
follow the directions for a particular visit, the sample should still be collected at that visit, and 
the date and 24-hour clock time of sample collection and the date and time of the 2 doses prior to 
the sample being drawn should be recorded. 
Only samples from patients receiving baricitinib will be assayed; samples from patients receiving 
placebo will not be assayed.  Pharmacokinetic samples will be kept in storage at a laboratory 
facility designated by the Sponsor.  Pharmacokinetic samples may also be assayed for additional 
exploratory analyses.  Pharmacokinetic results will not be provided to investigative sites until the 
completion of the study or to the blinded study team until the study has been unblinded. 
Bioanalytical samples collected to measure IP concentration will be retained for a maximum of 1 
year following last patient visit for the study. 
9.6. Pharmacodynamics  
Refer to Section 10.3.6. 
9.6.1. Whole Blood Samples for Pharmacogenetic Research  
A whole blood sample will be collected for pharmacogenetic analysis as specified in the 
Schedule of Activities (Section 2) where local regulations allow.   
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to baricitinib and to 
investigate genetic variants thought to play a role in 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 or its designee for a maximum of 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and/or ethical 
review boards (ERBs)/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 or after baricitinib becomes commercially available.   
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, and candidate gene studies.  Regardless of 
technology utilized genotyping data generated will be used only for the specific research scope 
described in this section.  
9.7. Biomarkers  
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics [PD], mechanism of action, variability of patient response 
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(including safety), and clinical outcome.  Sample collection is incorporated into clinical studies 
to enable examination of these questions through measurement of biomolecules including DNA, 
RNA, proteins, lipids, and other cellular elements. 
Blood samples for 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 or its designee for a maximum 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and ERBs 
impose shorter time limits.  This retention period enables use of new technologies, response to 
regulatory questions, and investigation of variable response that may not be observed until later 
in the development of baricitinib or after baricitinib becomes commercially available. 
9.8. Medical Resource Utilization and Health Economics  
The EQ-5D-Y is being utilized in this study to collect data for input into economic models.  See 
Section 9.1.4.11 for instrument description. 
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10. Statistical Considerations  
10.1. Sample Size Determination  
Approximately 25 patients will be enrolled into the Open-label PK Lead-in (Study Period 2) and 
may continue on open-label treatment during the long-term extension (Study Period 4).  Data 
from patients participating in the PK lead-in will be analyzed separately from patients 
randomized into the Double-blind treatment (Study Period 3).   
Study JAIP will aim to enroll at least 440 patients 2 to <18 years of age into the Double-blind 
Treatment period (Study Period 3), which includes at least 320 older pediatric patients (10 to 
<18 years) and at least 120 younger pediatric patients (2 to <10 years).  The proposed sample 
size (N=440) will ensure a >95% power to detect any difference between the baricitinib high 
dose and placebo treatment groups or the baricitinib medium dose and placebo treatment groups, 
each using a 2-sided alpha of 0.05, assuming a 10% placebo, 25% medium dose, and 30% high 
dose response rate for the primary endpoint using a chi-squared test.  The assumptions are based 
on what was observed in the Phase 2 study (JAHG).  The proposed end point of IGA 0 or 1 
represents patients whose AD is clear or almost clear from a baseline of moderate or severe 
disease.  The anticipated effect size represents 3 times more patients achieving this benefit 
compared to placebo which, in discussion with therapeutic experts, is of a magnitude that is 
considered to be clinically relevant. 
Furthermore, in older pediatric patients the sample size of 320 is sufficient to detect that the 
baricitinib high or medium dose is superior to placebo at least 80% of the time.  Similarly, in the 
younger pediatric patients, the planned sample size of 120 patients has > 80% simulated power 
using the Bayesian approach described in Section 10.3.7.3 and in the Study JAIP SAP to detect 
any difference between the baricitinib high dose or medium dose and placebo treatment groups 
with a probability threshold of 0.95.  
The primary analysis will be conducted using a logistic regression analysis with region, disease 
severity (IGA), age, treatment group, and treatment group-by-age interaction in the model.  The 
p-value and 95% confidence interval (CI) for the odds ratio from the logistic regression model 
are used for primary statistical inference.  The primary analysis will include data from the entire 
study population 2 to <18 years old, and a frequentist approach will be used for the analysis.  
However, in the event that the older subgroup of patients (10 to <18 years old) completes the 
Double-blind Treatment period (Study Period 3) more than 6 months earlier than anticipated for 
the younger subgroup of patients (2 to <10 years old), each age subgroup is adequately powered 
and can be individually unblinded and analyzed according to a pre-planned analysis approach as 
described in Section 10.3.8 below.  This is to ensure that potential delay in completing the 
enrollment of the younger patients will not delay analysis and submission of the data from the 
older patients. 
Sample size estimates were calculated using nQuery® Advisor 7.0 for the older subgroup of 
patients, and power estimates were obtained from R 3.5.0 and JAGS 4.2.0 for the younger 
subgroup of patients. 
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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.  Patients will be analyzed 
according to the treatment to which they were assigned.  Significant protocol violations will be 
described in the SAP. 
Safety analyses will be performed for all randomized patients who received at least 1 dose of IP 
and who did not discontinue from the study for the reason “Lost to Follow-up” at the first 
postbaseline visit. 
Safety analyses for the Post-treatment Follow-up period will be conducted on the follow-up 
population, defined as all randomized patients who received at least 1 dose of IP and entered the 
Post-treatment Follow-up period.  Patients will be analyzed according to the dosing regimen to 
which they were assigned in the Treatment Period. 
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 (CSR).  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 (e.g., refer to Section 10.3.7.3).  Treatment comparisons of discrete efficacy variables 
between baricitinib and placebo will be made using a logistic regression analysis with region, 
disease severity, age, treatment group, and treatment group-by-age interaction in the model.  The 
percentages, difference in percentages, and 95% confidence interval (CI) of the difference in 
percentages will be reported.  Treatment-by-age interaction will be added to the logistic 
regression 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 
effect) or qualitative (the treatment is beneficial for some but not all age groups).  The p-value 
from the Fisher exact test will also be produced. 
When evaluating continuous measures over time, a restricted maximum likelihood-based 
mixed-effects model of repeated measures (MMRM) will be used.  The model will include 
treatment, age cohort, baseline severity, visit, and treatment-by-visit interaction, and 
treatment-by-age cohort interaction as fixed categorical effects and baseline score and baseline 
score-by-visit interaction as fixed continuous effects.  Region may be included in the model if 
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applicable.  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 region, disease severity, treatment group, and 
baseline value in the model.  Type III tests for LSM will be used for statistical comparison 
between treatment groups.  The LSM difference, standard error, p-value, and 95% CI may also 
be reported.  The method used to handle missing data will be specified in the SAP. 
Fisher’s 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. 
Missing data imputation: 
1. 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 EASI 50/75/90 after discontinuation 
and onward.  Patients who receive rescue therapy will be analyzed as nonresponders after 
rescue and onward.  An additional analysis will be performed that includes all available 
data whether rescue medication was given or not. 
2. Continuous variables such as EASI and SCORAD scores will be assumed to be missing 
after rescue or discontinuation and then an MMRM analysis will be performed.  An 
additional analysis will be performed that includes all available data whether rescue 
medication was given or not. 
3. Last observed carried forward (LOCF).  An additional analysis will be performed that 
uses the last observed value on or 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. 
Additional sensitivity analyses for the primary and key secondary endpoints such as a reference 
based multiple imputation method may be performed and will be specified in the SAP. 
Adjustment for Multiple Comparisons: 
Multiplicity controlled analyses will be performed on the primary and major secondary endpoints 
to control the overall family-wise Type I error rate at a 2-sided α level of 0.05.  The graphical 
multiple testing procedure described in Bretz et al. (2011) will be used.  The graphical approach 
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is a closed testing procedure; hence it strongly controls the family-wise error rate across all 
endpoints (Alosh et al. 2014).  Each dose of baricitinib will be tested separately using the 
graphical approach.  Details of the specific graphical testing scheme (including testing for each 
dose of baricitinib and 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-treated patients (at each dose) achieving IGA of 0 or 1 and 
≥2-point improvement from baseline at Week 16. 
Key Secondaries Evaluated for Each Baricitinib Dose (high, medium, and low): 
 proportion of patients achieving EASI75 at 16 weeks 
 proportion of patients achieving EASI90 at 16 weeks 
 mean change from baseline in EASI score at 16 weeks 
 proportion of patients achieving SCORAD75 at 16 weeks 
 proportions of patients achieving a 4-point improvement in Itch NRS at 1 week, 2 weeks, 
4 weeks, and 16 weeks 
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, along with 
their reason for discontinuation.  Reasons for discontinuation from the study will be summarized 
by treatment group. 
10.3.2.2. Patient Characteristics  
Demographic and baseline characteristics will be summarized descriptively by treatment group.  
Descriptive statistics including number of patients, mean, standard deviation, median, minimum, 
and maximum will be provided for continuous measures, and frequency counts and percentages 
will be tabulated for categorical measures.  No formal statistical comparisons will be made 
among treatment groups unless otherwise stated. 
10.3.2.3. Concomitant Therapy  
Concomitant medications will be descriptively summarized by treatment group in terms of 
frequencies and percentages using the safety population.  The medications will be coded 
accordingly. 
10.3.2.4. Treatment Compliance  
Treatment compliance will be evaluated at every clinic visit.  A patient will be considered 
significantly noncompliant if he or she misses more than 20% of the prescribed doses during the 
study, unless the patient’s IP is withheld by the investigator for safety reasons; that is, 
compliance <80%.  Similarly, a patient will be considered significantly noncompliant if he or she 
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is judged by the investigator to have intentionally or repeatedly taken more than the prescribed 
amount of medication, that is, compliance ≥120%. 
10.3.3. Efficacy Analyses  
10.3.3.1. Primary Analyses  
The primary efficacy measure is the binary outcome of response defined as IGA score of 0 or 1 
(clear or almost clear skin) and ≥2-point improvement from baseline at Week 16.  The primary 
analysis will be conducted using a logistic regression analysis with region, disease severity 
(IGA), age, treatment group, and treatment group-by-age interaction in the model.  Nonresponder 
imputation for missing data as described above will be used.  
The primary analysis will include data from the entire study population 2 to <18 years old and 
will use a frequentist analysis approach.  However, in the event that the older subgroup of 
patients (10 to <18 years old) completes the Double-blind Treatment period (Study Period 3) 
more than 6 months earlier than the anticipated completion for the younger subgroup of patients 
(2 to <10 years old), each age subgroup will be unblinded and analyzed separately according to a 
pre-planned analysis approach as described in Section 10.3.8 below.  This is to ensure that 
potential delay in completing the enrollment of the younger patients will not delay analysis and 
submission of the data from the older patients. 
Additional analysis of the primary efficacy outcome will include analyzing the outcome as 
observed, that is, 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, that is, using the same logistic regression model.  Nonresponder imputation will be used 
for these analyses unless otherwise noted. 
 EASI75 at Week 16 and 1 year.  EASI75 is defined as having an improvement of at least 
75% from baseline.  Besides NRI, this outcome will also be analyzed using observed 
cases, that is, whether rescue medication was given or not. 
 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 and 1 year.  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. 
 IGA score of 0 or 1 (clear or almost clear skin) and ≥2-point improvement from baseline 
at Week 4 and 1 year. 
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 IGA of 0 at 16 weeks. 
 4-point improvement in Itch NRS at 1 week, 2 weeks, 4 weeks, and 16 weeks. 
The following continuous measures will be analyzed with the MMRM analysis described above 
unless otherwise noted.  Contrasts within the MMRM analysis 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: 
o ADSS Item 2 
o EASI score 
o SCORAD score 
o BSA 
o Itch NRS 
o Skin Pain NRS 
o POEM  
o PGI-S-AD 
o PROMIS-Depression 
o PROMIS-Anxiety 
o DFI 
o CDLQI and IDQOL total score 
o WPAI-AD-CG 
o EQ-5D-Y 
o PRISM 
 
Baricitinib tablet or oral suspension product acceptability and palatability during the PK lead-in 
period will be summarized categorically (frequency and percentage) by age group, for each visit 
separately and in aggregate. 
The EASI total score and SCORAD total score will also be analyzed as observed, that is, 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 TCS 
 Patients requiring rescue with systemic treatments 
 School days missed 
The following measures will be analyzed by an ANCOVA with treatment and baseline value in 
the model. 
 Mean number of days without use of TCS over 16 weeks 
 Mean gram quantity of TCS used over 16 weeks (tube weights) 
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10.3.3.3. Tertiary/Exploratory Analyses  
 Proportion of patients achieving IGA of 0 or 1 with a ≥2-point improvement at 2, 3, 4, 
and 5 years during long-term extension 
 Proportion of patients achieving EASI75 at 2, 3, 4, and 5 years during long-term 
extension  
 Proportion of patients achieving SCORAD75 at 2, 3, 4, and 5 years during long-term 
extension 
 Frequency of patient-reported “no itch” (Itch NRS score = 0) days from daily diaries 
from Week 12 to Week 16 
 Time to achieve a 4-point improvement in Itch NRS 
 Frequency of patient-reported “no pain” (Skin Pain NRS score = 0) days from daily 
diaries from Week 12 to Week 16 
 Mean change from baseline in the score of Item 1 of the ADSS at 1 week and 16 weeks  
 Mean change from baseline in the score of Item 3 of the ADSS at 1 week and 16 weeks 
 Changes from baseline in IgE levels during the study 
 Changes from baseline in eosinophil levels during the study 
 Characterization of baricitinib pharmacokinetics in the AD population and exploration of 
relationships between baricitinib exposure and study endpoints 
 Assessment of efficacy outcomes in patients who choose to take a voluntary drug 
interruption (drug holiday) during Study Period 4 
 Number of patients able to maintain control of AD signs and symptoms without use of 
TCS 
Details of the tertiary/exploratory analyses will be further described in the SAP. 
10.3.4. Safety Analyses  
All safety data will be descriptively summarized by treatment group and analyzed using the 
safety population. 
Treatment-emergent adverse events (TEAEs) are defined as AEs that first occurred or worsened 
in severity after the first dose of study treatment.  The number and percentage of patients who 
experienced at least 1 TEAE will be summarized using MedDRA (Medical Dictionary for 
Regulatory Activities) for each Preferred Term within System Organ Class by treatment group.  
Serious adverse events and AEs that led to permanent discontinuation from the IP will also be 
summarized by treatment group.  Special safety topics will be summarized and analyzed 
including the proportion and rate of patients developing skin infections requiring antibiotic 
treatment.  Fisher’s exact test will be used to perform comparisons between each baricitinib dose 
and the placebo group, where applicable. 
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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 laboratory variables obtained at baseline and postbaseline visits will be summarized 
along with change from baseline by treatment group.  Change from baseline to endpoint will be 
analyzed using ANCOVA with treatment and baseline value in the model.  Categorical variables, 
such as treatment-emergent laboratory abnormalities, will be summarized by frequency and 
percentage.  Shift tables will be presented for selected laboratory measures. 
Observed values and changes from baseline for vital signs and physical characteristics will be 
descriptively summarized by treatment group and time point.  Change from baseline to 
postbaseline in vital signs, height, and body weight will be analyzed using ANCOVA with 
treatment and baseline value in the model.  Treatment-emergent abnormalities in vital signs 
(pulse and blood pressure) and weight will be evaluated based on pediatric standards. 
A summary of temporary interruptions of study drug will be provided, showing the number of 
patients experiencing at least one temporary interruption and the number of temporary 
interruptions.  Duration of each temporary interruption and the cumulative duration of 
interruptions using descriptive statistics will be provided.   
Analyses of Growth (height, weight, and body mass index [BMI]): 
Observed height velocity by sex and age group will be calculated at baseline and approximately 
every 3 months thereafter throughout the study:  
 (Current Height [cm] - Previous Height [cm])/Interval (months) between 
Measurements × 12 
Age-specific z-scores for height velocity by sex and age group will be calculated for each patient 
with reference to standard height velocity tables (from age- and sex- matched peers) according to 
the following formula:  
 (Observed Height Velocity [cm/y] - Mean Height Velocity for Age and Sex 
[cm/y])/(standard deviation of reference population) 
Similar analyses for weight and BMI velocity and z-scores will be conducted.  
Data collected after initiation of rescue therapy will be summarized or listed where applicable. 
More details of the safety analysis for this study will be provided in the SAP. 
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses  
Open-label PK Lead-in (Study Period 2):  Serial PK sampling will be conducted to confirm that 
the high doses in pediatric age cohorts will produce comparable exposure to the 4-mg dose in 
adults.  Comparability will be assessed using non-compartmental methods (e.g., AUC and Cmax). 
Double-blind Treatment (Study Period 3):  All plasma baricitinib concentration–time data will be 
pooled and evaluated using population PK methods.  A covariate screen of patient and 
study-specific factors will be included in the analyses based on factors investigated in previous 
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and (if any) ongoing PK analyses and on their relevance to the target population.  Exploratory 
and/or model-based analyses examining the relationships between baricitinib exposure and 
efficacy and response endpoints will be conducted.  Other analyses of efficacy and safety 
outcome measures may also be assessed as scientifically appropriate and warranted by available 
data.  Details about the analyses to be conducted will be contained in the PK/PD analysis plan. 
10.3.6. Evaluation of Immunological Measures  
Patients who are immunized with TDaP or pneumococcal conjugate vaccines will have their IgG 
antibody titers to the antigens evaluated preimmunization and at 4 and 12 weeks 
postimmunization.  A primary immune response will be assessed in patients who have never 
received TDaP or pneumococcal conjugate vaccines previously, and secondary/booster responses 
will be assessed if the patients have previously received the vaccines.  More detailed analytical 
methods will be described in the SAP. 
10.3.7. Other Analyses  
10.3.7.1. Health Outcomes  
The health outcome measures will be analyzed using methods described for continuous or 
categorical data as described for efficacy measures in Section 10.3.3. 
10.3.7.2. Acceptability and Palatability  
Responses from the tablet and suspension acceptability and palatability questionnaires will be 
summarized categorically (frequency and percentage) by age group, for each visit separately and 
in aggregate.  In addition, general trends from baseline and Week 2 in acceptability and 
palatability will be analyzed. 
10.3.7.3. 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, the 
subgroup variable (e.g., age) and the subgroup by treatment interaction.  If the interaction is 
statistically significant at =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 variable of 
EASI, the MMRM analysis will include additional variables for subgroup and the subgroup by 
treatment interaction. 
Subgroups to be evaluated will include baseline disease severity, sex, age (<10 years or 
≥10 years), race, prior therapy (intolerance or inadequate response to TCS/TCNI), other atopic 
conditions (e.g., food allergies, asthma, allergic rhinitis/rhinoconjunctivitis).  Further definitions 
for the levels of the subgroup variables, the analysis methodology, and any additional subgroup 
analyses will be defined in the SAP.  Because this study is not powered for subgroup analyses, 
all subgroup analyses (with the exception of age cohorts, which are adequately powered) will be 
treated as exploratory. 
In the subgroup of older pediatric patients (10 to <18 years old), a frequentist approach will be 
used.  
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Younger Pediatric Patients (2 to <10 years old) 
In the subgroup of younger pediatric patients (2 to <10 years old), a hierarchical Bayesian 
analysis will be conducted using a logistic regression analysis as described above.  This logistic 
regression will also include covariate adjustments for disease severity (IGA) and treatment group 
in the model.  The posterior probability and 95% credible interval (CrI) for the difference in 
proportion from the logistic regression model are used for primary statistical inference.  Details 
of the Bayesian approach are described in the SAP. 
The analysis of the younger pediatric patients will leverage results observed in older pediatric 
patients through a Bayesian approach for the primary efficacy outcome at 16 weeks.  In this 
approach, the posterior distribution of the treatment response of baricitinib high dose in older 
pediatric patients will be used in the construction of a proper prior distribution for baricitinib 
high dose in younger pediatric patients which will be further described in the study JAIP SAP.  A 
similar approach will be used for the baricitinib medium and low doses in younger pediatric 
patients given that these doses are expected to provide exposures that are similar to their 
corresponding doses in older pediatric patients.  The statistical approach taken for the young 
pediatric patients is therefore grounded in (1) making best possible use of prospective patients’ 
data through efficient analysis procedures and (2) formally evaluating and modelling these data 
in light of the broader scientific context provided by existing information from older pediatric 
patients regarding patient outcomes on both the treatment and placebo regimens.  This is 
consistent with the EMA’s Reflection paper on the use of extrapolation in the development of 
medicines for pediatrics.  Furthermore, the methodology assures robust conclusions about 
efficacy of the investigational medicine in younger patients while ensuring the feasibility of the 
trial.   
Additionally, a consistency check will be conducted to determine whether the response for a 
specific treatment arm in the younger pediatric populations is within the 95% CI observed in 
older pediatric patients.  The planned sample size is 120 patients with 1:1:1:1 randomization.  
The planned sample size has >80% simulated power to detect any difference between the 
baricitinib high dose and placebo treatment groups or the baricitinib medium dose and placebo 
treatment groups with probability of at least 0.95 and that the observed effect is consistent with 
the effect seen in older pediatric patients.  This calculation relies on the assumption that 
leveraging information from older patients in Study JAIP is warranted.  If the consistency check 
is not satisfied, no information from the older cohort will be used.  In the event that the subgroup 
of younger pediatric patients has slow patient accrual, this will become the primary analysis for 
the younger patient subgroup.   
10.3.8. Interim Analyses  
No interim analyses are planned for this study.  The analysis of Study Period 3 data is considered 
to be the primary analysis.  If an unplanned interim analysis is deemed necessary, the appropriate 
Lilly medical director, or designee, will be consulted to determine whether it is necessary to 
amend the protocol.  Additional analyses in order to support regulatory submission may be 
required after patients have completed the primary endpoint during Study Period 3, and these 
additional analyses will be specified in the SAP. 
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In the event that the older subgroup of patients (10 to <18 years old) completes the Double-blind 
Treatment period (Study Period 3) more than 6 months earlier than the anticipated completion 
date for the younger subgroup of patients (2 to <10 years old), each age subgroup is adequately 
powered and can be individually unblinded and analyzed according to a pre-planned analytical 
approach.  In this pre-planned approach, the older subgroup of patients will be locked and 
analyzed (using a frequentist approach) after all patients in the subgroup have completed or 
discontinued from Study Period 3, and this analysis will be considered the primary analysis for 
the older subgroup.  Subsequently, after all patients in the younger subgroup have completed or 
discontinued from Study Period 3, the data from the younger subgroup will be locked and 
analyzed (using a Bayesian approach), and this analysis will be considered the primary analysis 
for the younger age subgroup.  The database lock and analysis of the data from the older 
subgroup of patients will not be considered an interim analysis and no alpha will be spent 
because the analysis of each age subgroup will be conducted independently and will be 
considered the primary analysis for the age group.  In this situation, the combined analysis of the 
entire study population (2 to <18 years old) will be considered a secondary analysis.  Further 
details of this pre-planned analytical approach will be included in the study JAIP SAP. 
10.3.8.1. Data Monitoring Committee  
A DMC will monitor the overall safety 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 pediatrics, 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 and growth data, etc.  The DMC may recommend continuation of the study as 
designed; temporary suspension of enrollment; or the discontinuation of a particular age cohort, 
dose regimen or the entire study.  While 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. 
Besides DMC members, a limited number of pre-identified individuals may gain access to the 
limited unblinded data from Study Period 3, as specified in the unblinding plan, prior to the 
database lock for the primary analysis or final database lock to initiate the final population 
PK/PD model development processes or for preparation of regulatory documents, respectively.  
Information that may unblind the study during the analyses will not be reported to study sites or 
the blinded study team until the study has completed. 
Unblinding details will be specified in a separate unblinding plan document. 
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10.3.8.2. Adjudication Committee  
A blinded external Clinical Event Committee will adjudicate potential MACE (cardiovascular 
death, myocardial intervention [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 and arterial thrombotic events, and 
noncardiovascular deaths.  Details of membership, operations, recommendations from the 
Committee, and the communication plan will be documented in the Charter. 
10.3.8.3. Unblinded Study Team for Regulatory Submission  
For the purpose of regulatory submission, a limited number of pre-identified individuals will 
have access to unblinded efficacy data when all the patients complete Week 16 assessments; 
hence, a portion of the long-term assessments may be unblinded prior to the final database lock.  
Only the blinded study team will communicate with sites on regular trial conduct issues, and 
study sites will not receive any efficacy and safety information on an individual patient level 
from this early analysis for regulatory submission. 
Besides DMC members and the Unblinded Study Team 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 final database lock for preparation of regulatory documents.  
Information that may unblind the study during the analyses will not be reported to study sites or 
the blinded study team until the study has completed. 
Unblinding details will be specified in a separate unblinding plan document to ensure proper 
firewalls between the unblinded study team and the blinded study team and study sites. 
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Bieber T. Atopic dermatitis. N Engl J Med. 2008;358(14):1483-1494. 
Bieber T. Atopic dermatitis. Ann Derm. 2010;22(2):125-137. 
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management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical 
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placebocontrolled, phase 3 trial. Lancet. 2017;389(10086):2287-2303.  
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 
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Broeders JA, Ahmed Ali U, Fischer G. Systematic review and meta-analysis of randomized 
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atopic dermatitis: A 15-year experience. J Am Acad Dermatol. 2016;75(2):410-419.e3. 
Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and 
initial validation of a new tool for measuring atopic eczema severity from the patients' 
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perspective [published correction appears in Arch Dermatol. 2005;141(3):381]. Arch 
Dermatol. 2004;140(12):1513-1519. 
Chavarro JE, Watkins DJ, Afeiche MC, Zhang Z, Sánchez BN, Cantonwine D, Mercado-García 
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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. 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
AUC 
area under the concentration curve 
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. 
BMI 
body mass index 
BSA 
body surface area 
CDLQI 
Children’s Dermatology Life Quality Index  
CI 
confidence interval 
Cmax 
maximum concentration 
CRF 
case report form 
CRP 
clinical research physician:  Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research scientist, 
global safety physician or other medical officer. 
C-SSRS 
Columbia Suicide Severity Rating Scale 
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CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DFI 
Dermatitis Family Impact  
DLQI 
Dermatology Life Quality Index 
DMC 
data monitoring committee 
EASI 
Eczema Area and Severity Index 
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. 
ePRO 
electronic patient-reported outcome 
EQ-5D-Y 
European Quality of Life-5 Dimensions-Youth version  
ERB 
ethical review board 
ETV 
early termination visit 
GCP 
good clinical practice 
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 
IDQOL 
Infant’s Dermatitis Quality of Life Index  
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IEC 
International Eczema Council 
IGA 
Investigator’s Global Assessment 
IGF-BP-3 
Insulin-like Growth Factor Binding Protein-3 
IL 
interleukin 
INR 
international normalized ratio 
Investigational 
product 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form. 
IV 
intravenous 
IWRS 
interactive web-response system 
JAK 
Janus kinase 
LOCF 
last observed carried forward 
LSM 
least squares mean 
MACE 
major adverse cardiovascular events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
myocardial infarction 
MMR 
measles, mumps, and rubella 
MMRM 
mixed-effects model of repeated measures 
MRI 
magnetic resonance imaging 
NEA 
National Eczema Association 
NRI 
nonresponder imputation 
NRS 
Numeric Rating Scale 
PBPK 
Physiologically Based Pharmacokinetic 
PD 
pharmacodynamics 
PDE-4 inhibitor 
phosphodiesterase type 4 inhibitor 
PeDRA 
Pediatric Dermatology Research Alliance 
PGI-S-AD 
Patient Global Impression of Severity–Atopic Dermatitis 
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PK 
pharmacokinetic 
POEM 
Patient-Oriented Eczema Measure 
PPD 
purified protein derivative 
PRISM 
Parent-Reported Itch Severity Measure 
PRO 
patient-reported outcome 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
QD 
once daily 
QoL 
quality of life 
RA 
rheumatoid arthritis 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCORAD 
SCORing Atopic Dermatitis 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
half life 
TB 
tuberculosis 
TBL 
total bilirubin level 
TCNI 
topical calcineurin inhibitor 
TCS 
topical corticosteroids 
TEAE 
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, which does not necessarily have to have a causal relationship 
with this treatment. 
TSH 
thyroid-stimulating hormone 
TSLP 
thymic stromal lymphopoietin 
TYK2 
tyrosine kinase 2 
ULN 
upper limit of normal 
vIGA-AD 
validated Investigator’s Global Assessment for Atopic Dermatitis 
VTE 
venous thromboembolic event (deep vein thrombosis or pulmonary embolism) 
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VZV 
varicella-zoster virus 
WPAI-AD-CG 
Work Productivity and Activity Impairment Questionnaire:  Atopic Dermatitis 
Caregiver 
 
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Appendix 2. 
Clinical Laboratory Tests  
Clinical Laboratory Tests 
Hematologya,b 
Clinical Chemistrya,b 
Hemoglobin 
Serum Concentrations of: 
Hematocrit 
Sodium 
Erythrocyte count (RBC) 
Absolute Reticulocyte Count 
Potassium 
Mean cell volume 
Mean cell hemoglobin 
Total bilirubin 
Mean cell hemoglobin concentration 
Direct bilirubin 
Leukocytes (WBC) 
Alkaline phosphatase 
Bone alkaline phosphatasel 
Platelets 
Alanine aminotransferase (ALT) 
Absolute counts of: 
Aspartate aminotransferase (AST) 
Neutrophils, segmented 
Blood urea nitrogen (BUN) 
Neutrophils, juvenile (bands) 
Creatinine 
Cystatin C 
Lymphocytes 
Uric acid 
Monocytes 
Calcium 
Eosinophils 
Glucose 
Basophils 
Albumin 
 
Total protein 
 
Estimated glomerular filtration rate (eGFR)e 
 
Creatine phosphokinase (CPK) 
Gamma-glutamyl transferase (GGT) 
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 
Gonadal hormone (estradiol for females, and 
testosterone for malesi  
 
Serum immunoglobulin (IgG, and IgE) 
IGF-1 and IGFBP-3 
Lipidsa,c 
QuantiFERON®-TB Gold or T-SPOT®.TB j 
Total cholesterol 
PPD (local testing) 
Low-density lipoprotein 
Baricitinib plasma levels 
High-density lipoprotein 
 
Triglycerides 
 
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Abbreviations:  HBV = hepatitis B virus; IGFBP-3 = insulin-like growth factor binding protein-3; 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 4 to 12 hours (depending on age 
and weight as specified in Section 9.4.3)  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. 
e For patients <18 years old, eGFR calculated by Bedside Schwartz 2009 formula.  For patients ≥18 years old, 
eGFR calculated 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 
(HCV RNA). 
h For all females 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 
Gonadal hormones will be collected for patients aged 8 to <18 years. 
j 
The QuantiFERON®-TB Gold test is the preferred alternative to the PPD test for the evaluation of TB infection.  
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.  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. 
l Collection of  a sample for bone alkaline phosphatase may be requested by the Sponsor as a reflex test if the 
alkaline phosphatase result is high. 
 
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Appendix 3. 
Study Governance Considerations  
 
 
 
 
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Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process 
Appendix 3.1.1. 
Informed Consent 
The investigator is responsible for: 
 ensuring that the patient and parent/caregiver or legal representative 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 and parent/caregiver 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 IP. 
 answering any questions the patient and parent/caregiver or legal representative may have 
throughout the study and sharing in a timely manner any new information that may be 
relevant to the patient and parent/caregiver or legal representative’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.  
A legal representative must give informed consent for a child to participate in this study.  In 
addition to informed consent given by the legal representative, the child may be required to give 
documented assent, if capable as specified by ethics board(s). 
Appendix 3.1.2. 
Recruitment 
Lilly or its designee is responsible for the central recruitment strategy for patients.  Individual 
investigators may have additional local requirements or processes. 
Appendix 3.1.3. 
Ethical Review 
The investigator or an appropriate local representative must give assurance that the ethical 
review board (ERB) was properly constituted and convened as required by International Council 
for Harmonisation (ICH) guidelines and other applicable laws and regulations. 
Documentation of ERB approval of the protocol and the ICF and Assent Form 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: 
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 the protocol and related amendments and addenda, current IB and updates during the 
course of the study 
 informed consent form and Assent 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 International Conference on Harmonisation (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 experience in treating pediatric AD patients 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 
The clinical study report (CSR) coordinating investigator will sign the final CSR for this study, 
indicating agreement that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study. 
Lilly will select a qualified investigator(s) from among investigators participating in the design, 
conduct, and/or analysis of the study to serve as the CSR coordinating investigator.  If this 
investigator is unable to fulfill this function, another investigator will be chosen by Lilly to serve 
as the CSR coordinating investigator. 
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. 
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Appendix 3.2. 
Data Quality Assurance 
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following: 
 provide instructional material to the study sites, as appropriate 
 provide 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 these instances where there is no prior written or electronic 
source data at the site, the ePRO/eCOA instrument record will serve as the source. 
If ePRO 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 or ECG data, will be stored electronically in the central vendor’s 
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database system.  Data will subsequently be transferred from the central vendor to the Lilly data 
warehouse. 
Any data for which paper documentation provided by the patient will serve as the source 
document will be identified and documented by each site in that site’s study file.  Paper 
documentation provided by the patient may include, for example, a paper diary to collect patient-
reported outcome (PRO) measures (for example, a rating scale), a daily dosing schedule, or an 
event diary. 
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system. 
Appendix 3.3. 
Study and Site Closure 
Appendix 3.3.1. 
Discontinuation of Study Sites 
Study site participation may be discontinued if Lilly, the investigator, or the ERB of the study 
site judges it necessary for medical, safety, regulatory, or other reasons consistent with 
applicable laws, regulations, and GCP. 
Appendix 3.3.2. 
Discontinuation of the Study 
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP. 
Appendix 3.4. 
Publication Policy 
The publication policy for Study I4V-MC-JAIP is described in Clinical Trial Agreement. 
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Appendix 4. 
Hepatic Monitoring Tests for Treatment-
Emergent Abnormality  
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly, or its designee, clinical 
research physician. 
Hepatic Monitoring Tests 
Hepatic Hematologya 
Haptoglobina 
Hemoglobin 
 
Hematocrit 
Hepatic Coagulationa 
RBC 
Prothrombin Time 
WBC 
Prothrombin Time, INR 
Neutrophils, segmented 
 
Lymphocytes 
Hepatic Serologiesa,b 
Monocytes 
Hepatitis A antibody, total 
Eosinophils 
Hepatitis A antibody, IgM 
Basophils 
Hepatitis B surface antigen 
Platelets 
Hepatitis B surface antibody 
 
Hepatitis B Core antibody 
Hepatic Chemistrya 
Hepatitis C antibody 
Total bilirubin 
Hepatitis E antibody, IgG 
Direct bilirubin 
Hepatitis E antibody, IgM 
Alkaline phosphatase 
 
ALT 
Anti-nuclear antibodya 
AST 
 
GGT 
Alkaline Phosphatase Isoenzymesa 
CPK 
 
 
 
Anti-smooth muscle antibody (or anti-actin 
antibody)a 
Abbreviations:  ALT = alanine aminotransferase; AST = aspirate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalized 
ratio; RBC = red blood cells; WBC = white blood cells. 
a Assayed by Lilly-designated or local laboratory. 
b Reflex/confirmation dependent on regulatory requirements and/or testing availability. 
 
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Appendix 5. 
Monitoring Tests for Confirmed VTE  
Selected tests may be obtained in the event of a confirmed venous thromboembolic event (VTE) 
and may be required in follow-up with patients in consultation with Eli Lilly and Company, its 
designee, or the 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 = clotting factor Xa; 
MTHFR = methylene tetrahydrofolate reductase; PT = prothrombin time; PTT = partial thromboplastin time. 
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Appendix 6. 
Administration of Efficacy, Safety, Health 
Outcomes, and Quality of Life Measures  
 
 
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The PRO assessments collected via eCOA device are shown in the order that they will be presented to the patient/parent.  PRO 
assessments collected via eCOA device at the site should be completed prior to any clinical assessments being performed on days 
when study visits occur.  Patients who turn 18 years old during the study will continue to provide information for the assessments.  
The version of the assessment initiated at baseline will not change for a patient during the study even if the patient changes age during 
the study.  
Assessment 
Collection 
Investigator or 
PRO 
Patient Age at Visit 1 (unless otherwise noted) 
SCORAD-VAS 
eCOA: at site 
PRO 
8 to <18 years: patient-rated (with help from caregiver as needed) 
2 to <8 years: parent/caregiver-rated with patient 
POEM 
eCOA: at site 
PRO 
8 to <18 years: Patient-rated (with help from caregiver as needed) 
2 to <8 years: Parent/caregiver-rated with patient 
CDLQI 
eCOA: at site 
PRO 
8 to <18 years: Patient-rated (with help from caregiver as needed) 
4 to <8 years: Parent/caregiver-rated with patient 
IDQOL 
eCOA: at site 
PRO 
2 to <4 years: parent/caregiver-rated 
PROMIS-Anxiety 
(collected only in countries 
where translations are available) 
eCOA: at site 
PRO 
8 to <18 years: patient-rated  
5 to <8 years: parent/caregiver-rated as proxy 
PROMIS-Depression 
(collected only in countries 
where translations are available) 
eCOA: at site 
PRO 
8 to <18 years: patient-rated  
5 to <8 years: parent/caregiver-rated as proxy 
EQ-5D-Y 
eCOA: at site 
PRO 
8 to <18 years: patient-rated  
4 to <8 years: parent/caregiver-rated as proxy 
DFI 
eCOA: at site 
PRO 
2 to <18 years: Parent/caregiver-rated 
WPAI-AD-CG 
eCOA: at site 
PRO 
2 to <18 years: Parent/caregiver-rated 
Palatability and Acceptability 
(only collected during Study 
Period 2, PK lead-in) 
paper: at site 
PRO 
10 to <18 years: patient-rated (tablets) 
2 to <10 years: parent/caregiver-rated (suspension) 
vIGA-AD 
paper: at site 
Investigator 
2 to <18 years 
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Assessment 
Collection 
Investigator or 
PRO 
Patient Age at Visit 1 (unless otherwise noted) 
EASI 
eCOA: at site 
Investigator 
2 to <18 years 
SCORAD 
eCOA: at site 
Investigator 
2 to <18 years 
C-SSRS 
Self-harm Supplement Form 
Self-harm Follow-up Form 
paper: at site 
Investigator 
7 to <18 years 
(if patient turns 7 years old during the study, C-SSRS collection will begin 
after patient turns 7 years old) 
PRISM 
eCOA: daily diary 
PRO 
2 to <10 years: parent/caregiver-rated 
Itch NRS 
eCOA: daily diary 
PRO 
10 to <18 years: patient-rated 
Skin Pain NRS 
eCOA: daily diary 
PRO 
10 to <18 years: patient-rated 
ADSS 
eCOA: daily diary 
PRO 
10 to <18 years: patient-rated 
PGI-S-AD 
eCOA: daily diary 
PRO 
10 to <18 years: patient-rated 
Emollient Reminder 
eCOA: daily diary 
PRO 
2 to <18 years: reminder only 
TCS Use 
eCOA: daily diary 
PRO 
10 to <18 years: patient-rated 
2 to <10 years: parent-caregiver-rated 
Missed School Days 
eCOA: daily diary 
PRO 
10 to <18 years: patient-rated 
2 to <10 years: Parent/caregiver-rated 
Abbreviations:  ADSS = Atopic Dermatitis Sleep Scale; CDLQI = Children’s Dermatology Life Quality Index; DFI = Dermatitis Family Impact; EASI = Eczema 
Area and Severity Index; eCOA = electronic clinical outcome assessment; EQ-5D-Y = European Quality of Life-5 Dimensions-Youth version; 
IDQOL = Infant’s Dermatitis Quality of Life Index; NRS = Numeric Rating Scale; PGI-S-AD = Patient Global Impression of Severity–Atopic Dermatitis; 
PK = pharmacokinetic; POEM = Patient Oriented Eczema Measure; PRISM = Parent-Reported Itch Severity Measure; PRO = patient-reported outcome; 
PROMIS = Patient-Reported Outcomes Measurement Information System; SCORAD = SCORing Atopic Dermatitis; TCS = topical corticosteroids; VAS = 
visual analogue scale; vIGA-AD = validated Investigator’s Global Assessment for Atopic Dermatitis; WPAI-AD-CG = Work Productivity and Activity 
Impairment Questionnaire:  Atopic Dermatitis Caregiver. 
 
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Appendix 7. 
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 9.4.9.1  Section 9.4.9.1 
Section 8.1.1  
Section 8.1.2  
ALT/AST 
≥2x ULN 
ALT ≥3x ULN ALT ≥5x ULN on 
≥2 consecutive 
tests 
>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 
(unless allowed 
after discussion 
with Sponsor) 
≥2x ULN 
(for patients 
with baseline 
<2x ULN) 
≥2x ULN on ≥2 
consecutive tests 
(for patients with 
baseline <2x 
ULN) 
No applicable 
criteria 
 
>3x ULN 
(unless allowed after 
discussion with Sponsor) 
 
>2.5x ULN AND TBL 
>2x ULN  
 
>2.5x ULN with 
symptomsa 
 
TBL 
≥1.5x ULN 
(unless allowed 
after discussion 
with Sponsor) 
≥2x ULN 
(for patients 
with baseline 
<1.5 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 8. 
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: 
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 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. 2014b;70(2):338-351. 
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Appendix 9. 
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 acetate 
Cream 1% 
 
 
Methylprednisolone acetate 
Cream 0.25% 
 
 
Hydrocortisone  
Lotion, cream, or ointment 2.5% 
Source:  WHO (1997) and Tadicherla et al. 2009 
 
 
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Appendix 10. Provisions for Changes in Study Conduct 
During Exceptional Circumstances  
Exceptional circumstances, such as pandemics or natural disasters, may cause disruptions to the 
conduct of the study.  Examples of such disruptions include limitations in the ability to conduct 
study procedures or ability to have on-site participant visits. 
To mitigate the risk of participants missing visits, to allow participants to safely continue in the 
study, and to maintain the data integrity of the study in the case of an exceptional circumstance, 
sites may implement changes to the conduct of the study on a case-by-case basis following 
sponsor’s written approval and if permitted by local regulations.  These provisions for 
changes in study conduct are temporary and will be repealed once the restrictions are lifted 
and the clinical site can comply with requirements of the protocol without the provisions 
described in this appendix.  Good clinical practice compliance and minimization of risks to 
study integrity are important considerations.  Ensuring the safety of study participants is the 
prevailing consideration. 
Additional written guidance will be provided by the sponsor in the event written approval is 
granted for changes in study conduct.  
The following changes in study conduct captured in this appendix will not be considered 
protocol deviations.  Missing data will be captured as protocol deviation(s). 
1. Remote visit (telephone/telemedicine) 
Telephone or technology-assisted virtual visits (telemedicine) to complete appropriate 
assessments are acceptable if in-person site visits are not possible.  The study site should 
capture the visit location and method with a specific explanation for any data missing 
because of missed in-person site visits in source document and eCRF.   
Examples of assessments that may be completed via telephone/telemedicine visit include the 
following: 
 AEs and product complaints  
 concomitant medications  
 review study participant diary (including study drug compliance)  
 C-SSRS (Since Last Visit Version), Self-Harm Supplement Form, and Self-Harm 
Follow-up Form (if applicable). 
2. Mobile home health visit 
Mobile visits may be performed as home visits (e.g., at participants’ homes) if travel to the 
site is not possible due to exceptional circumstances.  Mobile visits will be performed by a 
qualified home nursing service provider or trained site personnel, following sponsor written 
approval and if permitted by local regulations.  Procedures performed may include, but are 
not limited to, collecting blood and urine samples, conducting physical assessments, 
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administering PROs, and collecting health information.  Please note that requirements related 
to the reporting of SAEs remain unchanged.  Every effort should be made for the participant 
to return to on-site visits as soon as reasonably possible, while ensuring the safety of the 
participant and investigational site staff.  
Additional consent from the participant will be obtained for those who participate in home 
health services. 
3. Investigational product and ancillary supplies (including participant diaries) 
In cases when a patient is unable to come to the site to receive trial supplies during a normal 
on-site visit, the site should work with the sponsor to determine appropriate actions to receive 
trial supplies.  This may include a participant coming to the site to receive trial supplies only 
from site staff without full completion of a visit, a participant-approved designee coming to 
the site to receive trial supplies on a participant’s behalf, or delivery to a participant’s home.  
The following requirements must be met: 
 sponsor approves the alternative method of delivery, taking local regulatory 
requirements into consideration 
 participant consents verbally to alternate method of delivery   
 site confirms the participant’s receipt of the trial supplies 
 site/sponsor confirms appropriate ethics review board notification 
 alternate delivery of IP should be performed in a manner that does not compromise 
treatment blinding and ensures product integrity.  The existing protocol requirements 
for product accountability remain unchanged.  
 when delivering supplies to a participant’s home, 
o participant consent must include provision of any personal information 
o site/sponsor should ensure oversight of the shipping process to ensure 
accountability and product quality (i.e., storage conditions and intact 
packaging upon receipt) 
 additional instructions should be provided to the participant on how to return any 
unused or completed trial supplies. 
4. Local laboratory option 
In exceptional circumstances, to ensure patient safety and with the sponsor's prior written 
approval, local laboratory testing may be conducted in lieu of central laboratory testing.  The 
local laboratory must be qualified in accordance with local regulations.  Clinically significant 
laboratory findings must be recorded as an adverse event in the AE eCRF.  
5. Screening period guidance  
To ensure safety of study participants, laboratory values and other eligibility assessments 
taken at Visit 1 are valid for a maximum of 90 days.  Therefore, the following rules will be 
applied for participants who are paused in an active, nonrandomized status due to exceptional 
circumstances:   
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 Paused for less than 90 days from Visit 1 to Visit 2:  The participant will proceed to 
the next study visit per the Schedule of Activities in the protocol and Visit 2 
(randomization visit) must be conducted within 90 days from Visit 1.  
o The site should proceed with the next visit if eligibility criteria are confirmed 
and document the reason for delay in the eCRF. 
o Due to the pause in screening, sites should also reconfirm each participant’s 
consent and document in the source documentation. 
 Paused for more than 90 days from Visit 1 to Visit 2:  The participant must be 
discontinued from the study and rescreened.  The screening procedures per the 
Schedule of Activities in the protocol should be followed (starting at Visit 1) to 
ensure participant eligibility by randomization visit (Visit 2).  Before rescreening, the 
participant must sign a new ICF and receive a new identification number through 
IWRS.  Patients who screen fail due to enrollment being paused for more than 
90 days may rescreen within 4 weeks of the screen fail with specific guidance from 
the sponsor, and this will not be considered a protocol deviation.   
6. Increasing visit window(s) for primary and secondary endpoint visits 
 During Study Period 3 (post-randomization and up to but not including the primary 
endpoint [Visit 8]), visit windows may be extended up to a total of 28 days upon 
specific guidance from the sponsor.  
 Participants should complete primary endpoint visit (Visit 8/Study Period 3) and the 
final study endpoint visit (Visit 27/Study Period 4) as per original schedule whenever 
possible and safe to do so, at the investigator’s discretion.  However, in order to 
maximize the ability for such on-site visits, minimize missing data, and preserve the 
intended conduct of the study, the visit windows may be brought forward no sooner 
than 14 days or extended up to 28 days, upon specific guidance from the sponsor. 
 During the long-term extension (Study Period 4) and the Post-treatment follow-up 
(Visit 801/Study Period 5), visit windows may be extended up to 12 weeks upon 
specific guidance from the sponsor.  
 Upon specific guidance from the sponsor, assessments (e.g., x-rays) may be collected 
at visits not designated on the Schedule of Activities if the scheduled procedures were 
missed at visits when the patient could not attend an on-site visit. 
 For participants requiring the visit windows to be extended, additional study drug 
may need to be provided to avoid study drug interruption and maintain overall 
integrity of the trial.  Additional consent from the participant per local regulations 
will be obtained for those participants who will be dispensed additional study drug 
during the study treatment periods. 
7. Documentation  
a. Changes to study conduct 
Changes to study conduct will be documented as the following: 
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 Sites will need to identify and document the details of how all participants, visits 
methods, and activities conducted were affected by exceptional circumstances.  All 
dispensing/shipment records of IP and relevant communications, including 
delegation, should be filed with site trial records. 
 The site should document the participant’s verbal consent for having remote visits 
and remote dispensing of IP, ancillaries and diaries, prior to implementation of these 
activities.  
 Source document(s) that are generated at an off-site location (e.g., participant’s home) 
should be part of the investigator’s source documentation and should be transferred to 
the site in a secure and timely manner.  
b. Missing data and other protocol deviations  
The study site should capture specific explanation for any missing data and other protocol 
deviations in source documents and eCRF.  While protocol deviations may be 
unavoidable in an exceptional circumstance, documentation of deviations and missing 
data will be important for data analysis and reporting. 
Details of changes in analyses to specifically accommodate exceptional circumstances 
will be further described in the study SAP. 
8. Informing ERBs 
The sponsor and study investigators will notify ERBs as soon as possible to communicate 
implementation of changes in study conduct due to exceptional circumstances.  To protect the 
safety of study participants, urgent changes may be implemented before such communications 
are made, but all changes will be reported as soon as possible following implementation. 
 
 
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Appendix 11. Additional Procedures for Countries 
Participating in the PK Lead-in Period (Study Period 2)  
This appendix applies for countries participating in the PK lead-in period (Study Period 2) of 
Study JAIP.  Additions are designated using underline.  Deletions are designated using 
strikethrough. 
Additional venous blood samples for pharmacokinetic (PK) concordance testing (i.e., to assess 
concordance between PK micro blood samples and venous blood samples) have been included.  
In addition, clarification related to allowance for re-dispensing of open-label bottles of tablets 
during Study Period 2 has been included. 
Section 9.5. Pharmacokinetics 
Protocol Section 9.5.1. Open-label PK Lead-in (Study Period 2) 
Blood samples will be collected during the Open-label PK Lead-in period using a commercially 
available microsampling device (see Schedule of Activities below). These blood samples will be 
used to determine the concentrations of baricitinib using a validated bioanalytical method. The 
timing will be as follows: 
 At Visit 2 (Week 0/Day 1), patients will take their first dose of IP in the clinic, and PK 
samples will be collected 15 minutes and 1 hour postdose.  
 On Day 2 and thereafter: patients will take their IP once daily at home.  Patients should 
be instructed to take their dose at approximately the same time each day. 
 On Day 4, patients will take their IP at home, and PK samples will be collected at 2 hours 
and 4 hours postdose.  If PK samples are not collected on Day 4, they may be collected 
on the following days up to and including the date of Visit 3 (Week 1). 
 On Day 11, a PK sample will be collected BEFORE the IP is taken.  Immediately after 
the PK sample is collected, the patient will take the IP, and PK samples will be collected 
at 30 minutes and 6 hours postdose.  If PK samples are not collected on Day 11, they may 
be collected on the following days up to and including the date of Visit 4 (Week 2).  All 
PK samples must be completed before the patient leaves the clinical site at Visit 4. 
One patient in the older age group may be selected to provide 1 venous blood sample to assess 
concordance between venous blood samples and microsamples.  At least 5 patients in the older 
age group will be selected to provide 2 venous blood samples to assess concordance between 
venous blood samples and microsamples.  The venous blood samples for concordance testing 
will be collected at Visit 2 at the same time as the 1 hour microsample and at Visit 3 or 4 (on 
site) at the same time as one of the planned microsample collections. During Study Period 2, the 
actual date and 24-hour clock time of the PK sample collection, and the date and time of the last 
2 doses of IP will be recorded. For samples drawn on Day 4 and 11, the 2 previous doses should 
be the dose given on the day of the PK sample collection and the dose given the previous day. 
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5. Schedule of Activities  
 
Table JAIP.6. 
Schedule of Activities for Patients Participating in the Open-label PK Lead-in  
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
PTF/U 
 
Period 1 
Period 2 
Period 4 
Period 
5 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19/ 
ETa 
801 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
10
0 
112 
 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 
after last 
dose 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IWRS 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP tablets dispensed 
(patients ≥10 years old) 
  *The bottle dispensed 
at Visit 2 should be re-
dispensed at Visit 3 and 
4 (Study Period 2). 
 
X 
X* 
X* 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
IP suspension 
dispensed (patients <10 
years old) 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Baricitinib plasma 
concentration (PK 
sample)r 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
r PK samples will be collected as described in Section 9.5.1. 
 
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Appendix 12. EU-Specific Requirements  
In this appendix, additions are designated using underline.  Deletions are designated using 
strikethrough. 
12.1. 
-Specific Requirements  
This section provides the following additional information to investigators or their designees in 
the
 
 Hormonal contraception can only be prescribed to female patients of childbearing 
potential aged 15 years and over.  The investigator or his/her designee should alert the 
parents/caregivers of patients younger than 15 years of age of the possible adverse 
reactions to the fetus in case of pregnancy. 
 Total sexual abstinence is included in the list of highly effective birth control methods. 
 A QuantiFERON®-TB Gold test or the T-SPOT® TB test should be used for patients 
with known vaccination history with Bacillus Calmette–Guérin (BCG) vaccination.  The 
PPD test will remain an option for patients who do not have vaccination history with 
BCG vaccine.  This allows younger patients without a history of BCG vaccination to be 
enrolled where use of the QuantiFERON®-TB Gold test may exceed the blood volume 
restrictions. 
Section 6.1. Inclusion Criteria 
Patient Characteristics 
[8] are male or nonpregnant, nonbreastfeeding female patients 
Patients of childbearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex relationship 
(as part of their preferred and usual lifestyle) must agree to either remain 
abstinent or stay in a same-sex relationship without sexual relationships with 
the opposite sex. 
Total abstinence is defined as refraining from intercourse during the entirety 
of the study and for at least 4 weeks following the last dose of IP.  Periodic 
abstinence such as calendar, ovulation, symptothermal, post-ovulation 
methods and withdrawal are not acceptable methods of contraception. 
Otherwise, patients and their partners of childbearing potential must agree to use 
2 effective methods of contraception, where at least 1 form is highly effective for 
the entirety of the study and for at least 4 weeks following the last dose of IP. 
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In the
 hormonal contraception may be required (i.e., prescribed) 
only for female patients of childbearing potential aged 15 years and over.  The 
investigator or his/her designee should alert the parents/caregivers of patients 
younger than 15 years of age of the possible adverse reactions to the fetus in case 
of pregnancy. 
The following contraception methods are considered acceptable (the patient and 
their partner should choose 2, and 1 must be highly effective [defined as less than 
1% failure rate per year when used consistently and correctly]): 
 Highly effective birth control methods:   
o Combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation:  oral, 
intravaginal, or transdermal 
o Progestogen-only hormonal contraception associated with inhibition of 
ovulation:  oral, intravaginal or implantable 
o Intrauterine device (IUD)/intrauterine hormone-releasing system (IUS) 
o Vasectomized partner (with appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate). 
o Total sexual abstinence (as defined above) 
 Effective birth control methods:   
o Male or female condom with spermicide.  It should be noted that the 
use of male and female condoms as a double barrier method is not 
considered acceptable due to the high failure rate when these methods 
are combined. 
o Diaphragm with spermicide 
o Cervical sponge 
o Cervical cap with spermicide 
o Oral contraceptives that do not inhibit ovulation 
 
Note:  When local guidelines concerning highly effective or effective methods of 
birth control differ from the above, the local guidelines must be followed. 
Adolescent females who have started menses (even one cycle and any amount of 
spotting) are considered to be of childbearing potential. 
Females of nonchildbearing potential are not required to use birth control and they 
are defined as: 
o Females who are infertile due to surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis, or 
have not started menses (and are not sexually active) 
 
 
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Section 6.2. Exclusion Criteria 
Diagnostic Assessments 
[37] Patients with evidence of active TB or latent TB based on medical history and 
clinical features are excluded.  In addition, if the following criteria are met, 
the patient will be excluded: 
o positive PPD test (i.e., ≥5 mm induration between approximately 48 
and 72 hours after application, regardless of vaccination history), 
and/or 
▪ NOTE:  The PPD test should only be used in patients where blood 
volume restrictions do not allow for the use of the 
QuantiFERON®-TB Gold test or T-SPOT® TB test AND the 
patient does not have a history of BCG vaccination. 
o QuantiFERON®-TB Gold test or T-SPOT® TB test (as available and if 
compliant with local TB guidelines) may should be used instead of the 
PPD test unless blood volume restrictions do not allow for the use of 
the QuantiFERON®-TB Gold test or T-SPOT® TB test AND the 
patient does not have a history of BCG vaccination.  If the test results 
are positive, the patient will be excluded.  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 excluded. 
Section 9.4.7. Tuberculosis Testing 
Patients will be tested at screening (Visit 1) for evidence of active or latent TB as described in 
the exclusion criteria. Investigators should follow local guidelines for monitoring.  
The purified protein derivative (PPD) test will remain an option for patients who do not have 
vaccination history with BCG vaccine.  The rationale for allowing the PPD test is primarily for 
younger children where use of the QuantiFERON®-TB Gold test may exceed the blood volume 
restrictions, so in younger patients without a history of BCG vaccination, the PPD test would be 
acceptable. 
 
 
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Section 2. Schedule of Activities 
 Table JAIP.7. 
Schedule of Activities for Patients Participating in the Open-label PK Lead-in  
 
Screening 
Open-label PK Lead-in 
Long-term Extension Treatment 
PTF/U 
 
Period 1 
Period 2 
Period 4 
Period 
5 
Visit number 
1 
2 
3 
4 
Patient 
Transitions 
Directly to 
Visit 9 
(Period 4) 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19/ 
ETa 
801 
Weeks from initiation 
of baricitinib 
treatment  
 
0 
1 
2 
4 
12 
16 
28 
40 
52 
64 
76 
88 
10
0 
112 
 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 
after last 
dose 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB testd  
QuantiFERON®-TB 
Gold test or T-SPOT® 
TB test are preferred  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Read PPD if applicable 
(48–72 hours post 
PPD)e  
 
PPD test may be used 
only for patients 
without BCG 
vaccination AND for 
whom blood volume 
restrictions apply.   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
d TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®. 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. 
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). 
 
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Table JAIP.8. 
Schedule of Activities for Patients Randomized to Double-blind Treatment in Study Period 3  
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
PTF/U 
 
Period 1 
Period 3 
Period 4 
Period 5 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19/ 
ETa 
801 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 after 
last dose 
Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB testd  
QuantiFERON®-TB 
Gold test or T-SPOT® 
TB test are preferred  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Read PPD if applicable 
(48–72 hours post 
PPD)e  
 
PPD test may be used 
only for patients 
without BCG 
vaccination AND for 
whom blood volume 
restrictions apply.   
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
d TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®. 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. 
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).
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12.2. 
Specific Requirements  
This section includes regularly scheduled pregnancy tests for female patients in 
 and to 
clarify the reassessment of benefit-risk for patients to remain in the trial after Week 16. 
Section 2. Schedule of Activities 
The following modification has been made to Section 2; see Footnote n. 
 
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Table JAIP.2. 
Schedule of Activities for Patients Randomized to Double-Blind Treatment in Study Period 3 
 
… 
 
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from 
randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance 
interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
Laboratory 
Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancyn 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
n Pregnancy tests prior to first dose of investigational product for females ≥10 years old of age (<10 years at investigator discretion) if menarche reached or if 
there is reason to believe the patient is sexually active.  Pregnancy test results from Visit 2 must be known prior to first dose of investigational product.  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.  When the interval between scheduled visits exceeds 4 weeks, patients will undergo urine pregnancy self-testing at home 
approximately every 4 weeks (testing kits to be provided).  During these intervisit periods, the site will call the patient approximately every 4 weeks to obtain 
her pregnancy test results.  If required per local regulations and/or institutional guidelines, pregnancy testing can occur at other times during the study 
treatment period. 
  
 
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Section 5.1.4. Period 4: Long-Term Extension Treatment Period 
… 
All Patients: 
… 
The benefit/risk profile will be reassessed throughout the study and patients may be discontinued 
at any time.  In particular, during the long-term extension period, the investigators should 
continue to assess the benefit/risk profile of patients to remain in the trial after Week 16.  For a 
patient having safety and tolerability issues, or one who is not achieving adequate treatment 
response, investigators should use clinical judgment on whether to continue or discontinue 
patient participation in the study.
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Appendix 2. 
Clinical Laboratory Tests  
Clinical Laboratory Tests 
Hematologya,b 
Clinical Chemistrya,b 
Hemoglobin 
Serum Concentrations of: 
Hematocrit 
Sodium 
Erythrocyte count (RBC) 
Absolute Reticulocyte Count 
Potassium 
Mean cell volume 
Mean cell hemoglobin 
Total bilirubin 
Mean cell hemoglobin concentration 
Direct bilirubin 
Leukocytes (WBC) 
Alkaline phosphatase 
Bone alkaline phosphatasel 
Platelets 
Alanine aminotransferase (ALT) 
Absolute counts of: 
Aspartate aminotransferase (AST) 
Neutrophils, segmented 
Blood urea nitrogen (BUN) 
Neutrophils, juvenile (bands) 
Creatinine 
Cystatin C 
Lymphocytes 
Uric acid 
Monocytes 
Calcium 
Eosinophils 
Glucose 
Basophils 
Albumin 
 
Total protein 
 
Estimated glomerular filtration rate (eGFR)e 
 
Creatine phosphokinase (CPK) 
Gamma-glutamyl transferase (GGT) 
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 
Gonadal hormone (estradiol for females, and 
testosterone for malesi  
 
Serum immunoglobulin (IgG, and IgE) 
IGF-1 and IGFBP-3 
Lipidsa,c 
QuantiFERON®-TB Gold or T-SPOT®.TB j 
Total cholesterol 
PPD (local testing) 
Low-density lipoprotein 
Baricitinib plasma levels 
High-density lipoprotein 
 
Triglycerides 
 
Abbreviations:  HBV = hepatitis B virus; IGFBP-3 = insulin-like growth factor binding protein-3; PPD = purified 
protein derivative; RBC = red blood cell; TB = tuberculosis; WBC = white blood cell. 
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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 4 to 12 hours (depending on age 
and weight as specified in Section 9.4.3) 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. 
e eGFR calculated by Bedside Schwartz 2009 formula.  
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 
(HCV RNA). 
h For all females 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.  When the interval 
between scheduled visits exceeds 4 weeks, patients will undergo urine pregnancy self-testing at home 
approximately every 4 weeks (testing kits to be provided).  During these intervisit periods, the site will call the 
patient approximately every 4 weeks to obtain her pregnancy test results.  If required per local regulations and/or 
institutional guidelines, pregnancy testing can occur at other times during the study treatment period. 
i 
Gonadal hormones will be collected for patients aged 8 to <18 years. 
j 
The QuantiFERON®-TB Gold test is the preferred alternative to the PPD test for the evaluation of TB infection.  
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.  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. 
l Collection of  a sample for bone alkaline phosphatase may be requested by the Sponsor as a reflex test if the 
alkaline phosphatase result is high. 
 
 
 
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12.3. 
Specific Requirements  
This section provides the following additional information to investigators or their designees in 
: 
 Additional details on the strategies implemented to minimize patient pain and distress as 
much as possible. 
 Complete physical examinations to be conducted at additional time points. 
 Electrocardiograms to be conducted at additional time points. 
 Additional description of the Investigator’s Global Assessment (IGA) scale and 
investigator qualifications. 
 Additional requirements related to x-ray collection based on the feedback from the 
Bundesamt für Strahlenschutz (BfS) or
Federal Office for Radiation Protection. 
 Incorporated additional imaging requirements related to monitoring bone/cartilage 
growth based on the request from the Bundesinstitut für Arzneimittel und 
Medizinprodukte (BfArM) or Federal Institute for Drugs and Medical Devices. 
 Incorporated the addition of measurement of tibial length based on request from BfArM. 
 Incorporated option for knee x-ray if magnetic resonance imaging (MRI) of the knee is 
not possible. 
 Schedule of Activities was updated to be consistent with the treatment period in 
amendment b of the main protocol, JAIP. For clarity, text has been updated to make MRI 
collection consistent with x-ray collection by stopping when skeletal maturity has been 
confirmed by the investigator. 
 
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Section 2. Schedule of Activities 
Table JAIP.1. 
Schedule of Activities for Patients Randomized to Double-blind Treatment in Study Period 3 
 
Screening 
Double-blinded Treatment 
Long-term Extension Treatment  
 
Period 1 
Period 3 
Period 4 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
17 
18 
19 
Weeks from randomization 
 
0 
1 
2 
4 
8 
12 
16 
20 
24 
28 
40 
52 
64 
76 
88 
100 
112 
124 
Visit tolerance interval (days) 
-8 to -35 
 
±2 
±2 
±2 
±4 
±4 
±4 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
 Physical examinationu 
X 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (single) 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
X 
Left hand x-rayl 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
Tibial length measurement 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MRI of the knee (or x-ray of the knee if 
MRI is not possible)l, t 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
Long-term Extension Treatment  
PTF/U 
 
Period 4 – Extended  
(Patients Randomized to Double-Blind Treatment at Visit 2) 
Period 5 
Visit number 
20 
21 
22 
23 
24 
25 
26 
27s  
28s 
29s 
30s 
31s/ETa 
801 
Weeks from randomization 
136 
148 
160 
172 
184 
196 
208 
220 
232 
244 
256 
268 
 
Visit tolerance interval (days) 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
±7 
28 ±4 after 
last dose 
Physical examinationu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG (single) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Left hand x-rayl  
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Tibial length measurement 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
MRI of the knee (or x-ray of the knee if 
MRI is not possible)l, t 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
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Abbreviations:  ECG = electrocardiogram; ET = early termination; IP = investigational product; MRI = magnetic resonance imaging; PTF/U = post treatment 
follow up 
a An early termination visit should be conducted if patient discontinues from the study before Visit 27.  Visit 801 is the post-treatment follow-up visit, which 
occurs after the patient has been off IP for approximately 4 weeks.  Patients who have permanently discontinued IP but remain in the study for more than 
28 days without IP will only complete Visit 27/ET; Visit 801 (follow-up visit) is not required. 
l Left hand and knee x-rays or knee MRI at an early termination visit is are not required if previously taken within 6 months of the early termination visit.  For 
patients with radiologically proven completed skeletal maturity, left hand x-rays and knee x-rays or MRI are not required (see Section 9.4.9.3 below). 
t X-ray of the knee may be completed instead of MRI of the knee if MRI is not possible (see Section 9.4.9.3 below).   
u Symptomatic findings on bones and joints must be followed up appropriately by investigators. 
 
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Section 9. Study Assessments and Procedures 
Investigators will provide age-appropriate explanations to all children prior to any assessment or 
procedure.  Investigators should assess and monitor physical pain and distress at each visit. 
Section 9.1.1. Primary Efficacy Assessments 
Detailed description of the vIGA 
The IGA scale is proposed as primary endpoint in this program and measures the clinician’s 
impression of overall disease severity at a single time point.  In contrast to EASI and SCORAD, 
which are based on numerical scoring, IGA is intended to provide a snapshot of disease severity 
easily understandable by physicians and patients (e.g., ranging from clear skin to severe disease).  
The IGA is a commonly used scale in clinical trials in adult and pediatric patients.  The vIGA 
has been provided to other pharmaceutical industry sponsors and investigators at no cost with 
quick adoption by other sponsor companies in Phase 1, 2, and 3 clinical trials, broadening the use 
of the scale across clinical sites. 
The IGA used in this study is the vIGA-AD (referred to as the IGA throughout the protocol).  
For the purposes of this study, AD severity will be defined using the IGA.  The IGA scale with 
descriptors is shown below. 
Investigator’s Global Assessment (IGA) Scale  
0 – Clear:  No inflammatory signs of atopic dermatitis (no erythema, no induration/papulation, 
no lichenification, no oozing/crusting).  Post-inflammatory hyperpigmentation and/or 
hypopigmentation may be present. 
1 – Almost Clear:  Barely perceptible erythema, barely perceptible induration/papulation, and/or 
minimal lichenification.  No oozing or crusting. 
2 – Mild:  Slight but definite erythema (pink), slight but definite induration/papulation, and/or 
slight but definite lichenification.  No oozing or crusting. 
3 – Moderate:  Clearly perceptible erythema (dull red), clearly perceptible 
induration/papulation, and/or clearly perceptible lichenification.  Oozing and crusting may be 
present. 
4 – Severe:  Marked erythema (deep or bright red), marked induration/papulation, and/or marked 
lichenification.  Disease is widespread in extent.  Oozing or crusting may be present.  
Investigator Qualifications 
Investigators will be required to be certified to complete vIGA training for the JAIP study.  The 
certification process includes reviewing a video that describes the scale and provides guidance 
on how to rate patients and will use images of AD patients’ affected skin.  After reviewing the 
video, the PI must complete a certification examination including rating of 20 photographs of 
AD patients’ skin with descriptions of the area affected.  The investigators must pass the 
examination with a score of 70% or greater to receive certification as a vIGA rater for Study 
JAIP.  Investigators must be recertified approximately every 2 years. 
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Section 9.4.3. Laboratory Tests 
To minimize pain, distress, and fear, investigators will be trained and experienced in clinical 
research with children. Sampling will only be performed by trained staff as described below. 
Lilly will provide training to sites on blood sample volumes, in keeping with local procedures 
and standards of care. 
Blood sampling should be consolidated whenever possible.  With the exception of Visit 2 
(baseline), where 3 venipunctures will be needed (predose chemistry/hematology, and PK 
samples at 15 minutes and 1-hour postdose), it is anticipated that only 1 venipuncture will be 
required per visit in order to collect required blood tests.  The timing of sampling and number of 
sampling attempts should be minimized, in keeping with local guidelines and procedures.  For 
example, it is recommended that after one unsuccessful attempt, another experienced person 
should take over the procedure. 
Section 9.4.9.3. Growth Monitoring 
 Left hand x-rays will be collected to assess effects on bone age.  
o Left hand x-rays will be collected at the time points shown in the SOA above.  An 
appropriate physician at the clinical site will read the x-ray image, and if it is 
determined that the patient does not have growth potential (that is, the patient has 
completed skeletal maturity), then no further left hand x-rays will be required.  
That is, as soon as a left hand x-ray for a study patient shows mature skeletal 
findings, no further left hand x-rays are required for the patient for the remainder 
of the patient’s participation in the study.  The clinical sites will document the 
decision that a patient has reached skeletal maturity. 
 Magnetic resonance imaging (MRI) of the knee will be collected to monitor 
bone/cartilage growth. 
o MRI of the knee will be collected approximately every 6 months as shown in the 
SoA above.  A central vendor will be used for reading of MRI images.  An 
appropriate physician at the clinical site will read the MRI image, and if it is 
determined that the patient does not have growth potential (that is, the patient has 
completed skeletal maturity), then no further knee MRI will be required.  The 
clinical sites will document the decision that a patient has reached skeletal 
maturity.  
o An x-ray of the knee (anteroposterior) may be collected in place of the MRI in 
cases where MRI is not possible (e.g., site does not have MRI access; sedation is 
required; MRI is not medically advisable in the opinion of the investigator; or 
parents/patients do not consent).  The clinical site will document the rationale for 
collecting x-rays versus MRIs.  An appropriate physician at the clinical site will 
read the x-ray image, and if it is determined that the patient does not have growth 
potential (that is, the patient has completed skeletal maturity), then no further 
knee x-rays will be required.  The clinical sites will document the decision that a 
patient has reached skeletal maturity. 
 Tibial length measurement will be collected as an additional assessment of growth. 
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o Tibial length will be measured approximately every 3 months as shown in the 
SOA above.  Guidance on measuring tibial length will be provided by the 
Sponsor. 
 
 
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Appendix 13. Guidance for Blood Sampling When Volume 
Restrictions May Apply  
This appendix applies for all countries participating in Study JAIP and is anticipated to be 
applicable for patients 2 to <8 years old and particularly for patients 10 to <20 kg in body 
weight; however, it may be used for older patients if local regulations require restrictions on 
blood volumes. 
Due to blood volume restrictions, some laboratory samples may not be collected (for example, 
exploratory storage samples and genetic and biomarker samples).  Laboratory samples should be 
collected as described in a sponsor-provided weight-based prioritization chart.  
Additional allowances to accommodate blood volume restrictions may include, but are not 
limited to the following: 
 Blood draws for Visit 1 and Visit 2 may be divided over 2 days if the 24-hour blood 
volume limit is exceeded. 
 The pharmacogenetics (DNA) sample may be collected after Visit 1 at the earliest visit 
where blood volumes allow. 
 HBV DNA will be collected as a reflex test prior to Visit 2 and is only required for 
patients who are positive for hepatitis B core antibody (HBcAb).  
 HCV RNA will be collected as a reflex test prior to Visit 2 and is only required for 
patients who are positive for HCV antibody. 
 
 
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Appendix 14. Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Amendment [b]: (06-Aug-2020) 
Overall Rationale for the Amendment 
Protocol I4V-MC-JAIP - A Phase 3, Multicenter, Randomized, Double-blind, 
Placebo-controlled, Parallel-group, Outpatient Study Evaluating the Pharmacokinetics, Efficacy, 
and Safety of Baricitinib in Pediatric Patients with Moderate-to-Severe Atopic Dermatitis- has 
been amended.  The new protocol is indicated by amendment (b) and will be used to conduct the 
study in place of any preceding version of the protocol. 
The overall changes and rationale for the changes made to this protocol are described in the 
following table.  Editorial revisions with no impact on protocol design or implementation were 
also made.  These revisions are not noted in this protocol amendment summary except where 
contained in a section with substantive changes. 
There are 3 main changes incorporated into this protocol amendment: 
 Addition of knee imaging and increased frequency of hand x-ray requirements related to 
monitoring bone growth and clarification of assessment of any symptomatic areas of 
bones/joints were included based on regulatory feedback.  In addition, baseline 
assessment of sexual maturation was included based on regulatory feedback. 
 Extension of the duration of treatment for all patients. 
 Guidance for study implementation under exceptional circumstances, such as pandemics 
or natural disasters. 
Amendment Summary for Protocol I4V-MC-JAIP Amendment (b) 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1  Synopsis 
Section 2 Schedule of Activities 
Section 3.3 Benefit/Risk 
Assessment 
Section 4 Objectives and 
Endpoints 
Section 5.1 Overall Design 
Section 8.2 Discontinuation from 
the Study 
Section 10.3.3.2 Secondary 
Analyses  
Section 10.3.3.3 
Tertiary/Exploratory Analyses 
  
Increased the treatment period from 2 
to 4 years, additional exploratory 
objectives were included for 
timepoints in the extended treatment 
period, and relevant updates were 
included to describe possible 
termination of the study in a specific 
geography after commercial 
availability or negative regulatory 
opinion. 
 
 
 
Based on data from completed 
adult Phase 3 studies and initial 
data from Study JAIP which 
support risk/benefit in pediatric 
patients, the treatment period was 
increased from 2 to 4 years.  
Secondary and 
tertiary/expoloratory IGA and 
EASI objectives were aligned with 
this change.  This extension of 
treatment will allow 
for continued efficacy and safety 
data collection and will allow 
patients to continue to receive 
baricitinib treatment for up to an 
additional 2 years until baricitinib 
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Section # and Name 
Description of Change 
Brief Rationale 
is commercially available for this 
population or not approved. 
Clarification was added related to 
termination of the study in a 
specific geography after 
commercial availability of 
baricitinib in that geography or 
after negative regulatory opinion. 
Section 2 Schedule of Activities 
Section 9.4.3 Laboratory Tests 
Appendix 10 
  
Added provisional language for 
participation in the study during 
exceptional circumstances such as the 
Coronavirus disease 2019 (COVID-
19) pandemic.  
 
Included provision for home visits to 
collect laboratory tests. 
Appendix 10 describes the types 
of changes to study conduct that 
will be possible during 
exceptional circumstances.  These 
changes to study conduct will only 
be implemented with approval 
from the sponsor and if permitted 
by local regulations. Provision 
was made for home visits for 
patient convenience specifically to 
collect laboratory tests during the 
study if approved by the sponsor 
and if permitted by local 
regulations. 
Section 2 Schedule of Activities 
Section 9.4.4.1 Tanner Staging 
Scale  
Section 9.4.9.3 Growth 
Monitoring  
 
Addition of knee imaging 
approximately every 6 months. 
 
Increased frequency of hand x-ray to 
approximately every 6 months.  
 
Added baseline Tanner Staging Scale. 
Imaging procedures were included 
or increased in frequency based on 
feedback from regulatory agencies 
for additional monitoring of bone 
growth and assessment of 
symptomatic areas of bones/joints.  
Baseline assessment of sexual 
maturity (Tanner Staging) was 
included based on feedback from 
regulatory agencies. 
Section 11 References 
Addition of references for Tanner 
Staging  
References to support addition of 
Tanner Staging were included. 
 
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