A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Adult Patients With Atopic Dermatitis
Phase: PHASE3
Conditions: Atopic Dermatitis
Sponsor: Eli Lilly and Company

Clinical Study Protocol Version (c) I4V-MC-JAHN 
 
A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and Efficacy of 
Baricitinib in Adult Patients with Atopic Dermatitis 
NCT03334435 
Approval Date: 27-Nov-2019 

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Protocol I4V-MC-JAHN(c)
A Phase 3 Multicenter, Double-Blind Study to Evaluate the 
Long-Term Safety and Efficacy of Baricitinib in Adult 
Patients with Atopic Dermatitis
BREEZE-AD3
EudraCT Number:  2017-000873-35
Baricitinib (LY3009104)
A 4-year Phase 3 multicenter, double-blind long-term extension study to evaluate the safety 
and efficacy of placebo, baricitinib 1-mg, baricitinib 2-mg, and baricitinib 4-mg in adult 
patients with atopic dermatitis, including a blinded randomized treatment withdrawal and 
randomized downtitration.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly:  25 Jul 2017
Amendment (a) Electronically Signed and Approved by Lilly:  15 Dec 2017
Amendment (b) Electronically Signed and Approved by Lilly:  29 Mar 2019
Amendment (c) Electronically Signed and Approved by Lilly on approval date provided 
below
Approval Date: 27-Nov-2019 GMT

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Table of Contents
Section
Page
Protocol I4V-MC-JAHN(c) A Phase 3 Multicenter, Double-Blind Study to 
Evaluate the Long-Term Safety and Efficacy of Baricitinib in Adult 
Patients with Atopic Dermatitis...........................................................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................13
3.
Introduction ......................................................................................................................17
3.1.
Background..................................................................................................................17
3.2.
Study Rationale............................................................................................................18
3.3.
Benefit/Risk Assessment..............................................................................................18
4.
Objectives and Endpoints..................................................................................................19
5.
Study Design.....................................................................................................................21
5.1.
Overall Design .............................................................................................................21
5.1.1.
Screening and Baseline Period .............................................................................23
5.1.2.
Treatment Period 1:  0 to 52 Weeks......................................................................23
5.1.2.1.
Responders and Partial Responders.................................................................23
5.1.2.2.
Nonresponders................................................................................................24
5.1.3.
Treatment Period 2:  52 to 200 Weeks..................................................................24
5.1.3.1.
Substudy at Week 52:  Randomized Withdrawal and 
Downtitration .................................................................................................24
5.1.3.2.
Patients Not Entered into the Substudy ...........................................................25
5.1.4.
Post-treatment Follow-up Period..........................................................................25
5.2.
Number of Participants.................................................................................................26
5.3.
End of Study Definition ...............................................................................................26
5.4.
Scientific Rationale for Study Design...........................................................................26
5.5.
Justification for Dose ...................................................................................................26
5.5.1.
Dose Adjustment for Renal Impairment ...............................................................27
6.
Study Population...............................................................................................................28
6.1.
Inclusion Criteria..........................................................................................................28
6.2.
Exclusion Criteria ........................................................................................................29
6.3.
Lifestyle Restrictions....................................................................................................29
6.4.
Screen Failures.............................................................................................................30
7.
Treatments........................................................................................................................31
7.1.
Treatments Administered .............................................................................................31

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7.1.1.
Packaging and Labeling .......................................................................................32
7.2.
Method of Treatment Assignment ................................................................................32
7.2.1.
Selection and Timing of Doses.............................................................................32
7.2.2.
Dose Adjustment for Renal Impairment ...............................................................32
7.3.
Blinding .......................................................................................................................33
7.4.
Dosage Modification....................................................................................................34
7.5.
Preparation/Handling/Storage/Accountability...............................................................34
7.6.
Treatment Compliance .................................................................................................34
7.7.
Concomitant Therapy...................................................................................................34
7.7.1.
Topical Corticosteroids and Other Topical Treatments.........................................34
7.7.2.
Other Permitted Medications and Procedures .......................................................35
7.7.3.
Prohibited Medications and Procedures................................................................36
7.8.
Treatment after the End of the Study............................................................................37
7.8.1.
Continued Access.................................................................................................37
8.
Discontinuation Criteria ....................................................................................................38
8.1.
Discontinuation from Study Treatment.........................................................................38
8.1.1.
Temporary Interruption from Study Treatment.....................................................38
8.1.2.
Permanent Discontinuation from Study Treatment ...............................................39
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................41
8.2.
Discontinuation from the Study....................................................................................41
8.3.
Lost to Follow-Up........................................................................................................41
9.
Study Assessments and Procedures ...................................................................................43
9.1.
Efficacy Assessments...................................................................................................43
9.1.1.
Investigator’s Global Assessment.........................................................................43
9.1.2.
Eczema Area and Severity Index Scores...............................................................43
9.1.3.
SCORing Atopic Dermatitis.................................................................................43
9.1.4.
Health Outcomes and Quality-of-Life Measures...................................................43
9.1.4.1.
Patient-Oriented Eczema Measure ..................................................................44
9.1.4.2.
Itch Numeric Rating Scale..............................................................................44
9.1.4.3.
Atopic Dermatitis Sleep Scale ........................................................................44
9.1.4.4.
Skin Pain Numeric Rating Scale .....................................................................44
9.1.4.5.
Patient Global Impression of Severity.............................................................44
9.1.4.6.
Dermatology Life Quality Index.....................................................................44
9.1.4.7.
European Quality of Life – 5 Dimensions – 5 Levels......................................45
9.1.4.8.
Work Productivity and Activity Impairment 
Questionnaire – Atopic Dermatitis..................................................................45
9.1.5.
Appropriateness of Assessments ..........................................................................45
9.2.
Adverse Events ............................................................................................................45

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9.2.1.
Serious Adverse Events........................................................................................46
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................47
9.2.2.
Adverse Events of Special Interest .......................................................................47
9.2.3.
Complaint Handling.............................................................................................47
9.3.
Treatment of Overdose.................................................................................................48
9.4.
Safety...........................................................................................................................48
9.4.1.
Vital Signs ...........................................................................................................48
9.4.2.
Physical Exam .....................................................................................................48
9.4.3.
Laboratory Tests ..................................................................................................48
9.4.4.
Hospital Anxiety Depression Scale.......................................................................48
9.4.5.
Columbia-Suicide Severity Rating Scale ..............................................................48
9.4.6.
Self-Harm Supplement and Follow-Up Form .......................................................49
9.4.7.
Hepatitis B Virus DNA Monitoring......................................................................49
9.4.8.
Hepatic Safety Monitoring and Data Collection....................................................49
9.4.9.
Safety Monitoring ................................................................................................50
9.5.
Pharmacokinetics .........................................................................................................51
9.6.
Pharmacodynamics ......................................................................................................51
9.7.
Pharmacogenetics.........................................................................................................51
9.8.
Biomarkers...................................................................................................................51
9.9.
Medical Resource Utilization and Health Economics ...................................................51
10.
Statistical Considerations ..................................................................................................52
10.1. Sample Size Determination ..........................................................................................52
10.2. Populations for Analyses..............................................................................................52
10.3. Statistical Analyses ......................................................................................................52
10.3.1.
General Statistical Considerations ........................................................................52
10.3.2.
Treatment Group Comparability...........................................................................54
10.3.2.1.
Patient Disposition..........................................................................................54
10.3.2.2.
Patient Characteristics ....................................................................................54
10.3.2.3.
Concomitant Therapy .....................................................................................54
10.3.2.4.
Treatment Compliance....................................................................................54
10.3.3.
Efficacy Analyses ................................................................................................55
10.3.4.
Safety Analyses....................................................................................................55
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................56
10.3.6.
Other Analyses.....................................................................................................56
10.3.6.1.
Subgroup Analyses.........................................................................................56
10.3.7.
Interim Analyses..................................................................................................56
10.3.7.1.
Data Monitoring Committee ...........................................................................56
10.3.7.2.
Adjudication Committee.................................................................................57

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11.
References ........................................................................................................................58
12.
Appendices .......................................................................................................................61

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List of Tables
Table
Page
Table JAHN.1.
I4V-MC-JAHN Schedule of Activities...........................................................13
Table JAHN.2.
Objectives and Endpoints...............................................................................19
Table JAHN.3.
Treatment Regimens......................................................................................31
Table JAHN.4.
Criteria for Temporary Interruption of Investigational Product.......................38

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List of Figures
Figure
Page
Figure JAHN.1. Illustration of study design for clinical Protocol I4V-MC-JAHN....................22

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................62
Appendix 2.
Study Governance Considerations..................................................................65
Appendix 3.
Clinical Laboratory Tests...............................................................................69
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................70
Appendix 5.
Liver Function Testing and Hepatic Safety Monitoring..................................71
Appendix 6.
Classification of Potency for Topical Corticosteroids.....................................72
Appendix 7.
Monitoring Tests for Confirmed VTE............................................................73
Appendix 8.
Protocol Amendment I4V-MC-JAHN(c) Summary - A Phase 3 
Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and 
Efficacy of Baricitinib in Adult Patients with Atopic Dermatitis ....................74

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1. Synopsis
Title of Study:
A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-Term Safety and Efficacy of Baricitinib in Adult 
Patients with Atopic Dermatitis
Rationale:
Atopic dermatitis (AD) is a pruritic, chronic or chronically relapsing, highly symptomatic inflammatory skin disease 
characterized by excessive T cell activation leading to significant skin infiltration by T cells and dendritic cells 
(Bieber 2010).  Presentation is varied, but includes skin manifestations and pruritus, with associated sleep 
disturbances.  The course of disease includes relapses of varying duration and severity.
Baricitinib is an oral 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, interleukin (IL)-13, IL-5, IL-4, IL-22, and IL-31, many of which activate 
receptors with downstream signaling through intracellular JAK1/JAK2/TYK2 (Nomura and Kabashima 2015).  This 
activity profile suggests that baricitinib may inhibit cytokines involved in AD pathogenesis.
Clinical studies have established that baricitinib is effective in autoimmune and autoinflammatory diseases involving 
the joints, kidneys, and skin.  Baricitinib was effective in reducing swollen and tender joints in patients with 
rheumatoid arthritis (Genovese et al. 2016; Dougados et al. 2017; Fleischmann et al. 2017; Taylor et al. 2017), was 
effective in reducing disease severity in patients with moderate to severe plaque psoriasis (Papp et al. 2016), and 
was effective in reducing the urinary albumin-to-creatinine ratio in patients with diabetic kidney disease (Tuttle et al. 
2015).  In addition, in a recently completed Phase 2 study (I4V-MC-JAHG), baricitinib was effective in reducing 
disease severity in patients with moderate to severe AD. The mechanism of action, combined with demonstration of 
clinical benefit in inflammatory diseases involving joints, kidneys, and skin, provides the rationale for evaluating 
baricitinib in moderate to severe AD.
Objectives/Endpoints:
Objectives
Endpoints
Primary
To estimate the effect of long-term therapy with 
baricitinib on responders and partial responders at 
entry of JAHN.

Proportion of patients with a response of IGA 0 or 
1 assessed at Weeks 16, 36, and 52
Secondary (Weeks 0–52)
Baricitinib Patients at Entry to Study JAHN
To evaluate the effect of increasing or maintaining 
baricitinib dose on clinical measures and 
patient-reported outcomes.

Proportion of patients with a response of IGA 0, 1,
or 2 assessed at Weeks 16, 36, and 52

Proportion of patients with a response of IGA 0 or 
1 assessed at Weeks 16, 36, and 52 
(nonresponders)

Proportion of patients achieving response of 
EASI75 from baseline of originating study 
assessed at Weeks 16, 36, 52

Proportion of patients with a 4-point improvement 
from baseline of originating study in Itch NRS at 
16 weeks

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Objectives
Endpoints
Placebo Nonresponders at Entry to Study JAHN
To evaluate the effect of starting baricitinib 2-mg 
versus 4-mg on clinical measures and 
patient-reported outcomes.

Proportion of patients with a response of IGA 0, 1,
or 2 assessed at Weeks 4, 16, 24, 52

Proportion of patients with a response of IGA 0 or 
1 assessed at Weeks 4, 16, 24, 52

Proportion of patients achieving response of 
EASI75 from baseline of originating study 
assessed at Weeks 4, 16, 24, 52

Proportion of patients with a 4-point improvement 
from baseline of originating study in Itch NRS at 
16 weeks
Secondary (Weeks 52–104)
All Patients Entering the Substudy
To evaluate the change in clinical response after 
treatment withdrawal or downtitration.
Patients Entering the Substudy with IGA 0 or 1
To evaluate the change in clinical response after 
treatment withdrawal or downtitration.

Proportion of patients with a response of IGA 0, 1,
or 2 assessed at 16 weeks after rerandomization
(Week 68) and Week 104

Proportion of patients with a response of IGA 0 or 
1 assessed at 16 weeks after rerandomization
(Week 68) and Week 104

Proportion of patients with a response of EASI75 
from baseline of originating study assessed at 
16 weeks after rerandomization (Week 68) and 
Week 104

Time to retreatment (time to IGA ≥3)
Patients Retreated During Substudy
To evaluate the ability to recapture efficacy based on 
clinical measures after experiencing a loss of 
treatment benefit:

Proportion of patients with a response of IGA 0, 1,
or 2 within 16 weeks of retreatment

Proportion of patients with a response of IGA 0 or 
1 within 16 weeks of retreatment

Proportion of patients with a response of EASI75 
from baseline of originating study within 16 weeks 
of retreatment
Patients Not Entered into the Substudy
To evaluate the effect of maintaining baricitinib dose 
on clinical measures.

Proportion of patients with a response of IGA 0, 1,
or 2 assessed at Week 104

Proportion of patients with a response of IGA 0 or 
1 assessed at Week 104

Proportion of patients with a response of EASI75 
from baseline of originating study assessed at 
Week 104
Abbreviations:  EASI = Eczema Area and Severity Index; IGA = Investigator’s Global Assessment; NRS = numeric 
rating scale.
Summary of Study Design:
Study I4V-MC-JAHN (JAHN) is a Phase 3, multicenter, double-blind study to evaluate the long-term safety and 
efficacy of baricitinib (1-mg once daily, 2-mg once daily, and 4-mg once daily) in adult patients with AD for up to 
4 years. The study population will include patients aged 18 years or older who completed an originating study (such 
as I4V-MC-JAHL, I4V-MC-JAHM, or 14V-MC-JAIY) and were eligible for enrollment into JAHN.  There is a 
single substudy included that will evaluate treatment withdrawal and dose downtitration.

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Treatment Arms and Duration:
The treatment study duration will be up to 4 years.  The study consists of 3 study periods and 1 substudy:  
randomized treatment withdrawal and downtitration.
Screening and Baseline Period: For most patients, the last visit of the originating study will be the first visit and 
screening/baseline period for Study JAHN.  Patients still completing a washout from systemic therapies from 
originating study will have this period extended for a maximum of 8 weeks and have their baseline established after 
washout is completed.  At baseline, patients will be classified into the following groups based on their response to 
treatment in the originating study: “Responders (Investigator’s Global Assessment [IGA] 0 or 1 and never rescued)
and Partial Responders (IGA 2 and never rescued)” or “Nonresponders (IGA 3 or 4 or rescued).”
Treatment Period:  The full treatment period will last from Week 0/Visit 1 through Week 200/Visit 22.  Patients will 
continue using emollients daily and topical corticosteroid (TCS) use will be permitted at the investigator’s discretion 
and provided automatically at the time of rescue or retreatment.
Treatment Period 1:  Week 0 (Visit 1) up to Week 52 (Visit 8):
At Week 0/Visit 1:

Nonresponders receiving placebo, baricitinib 1-mg, or baricitinib 2-mg in the originating study will be 
rerandomized in a blinded fashion 1:1 to either baricitinib 2-mg or baricitinib 4-mg.  Nonresponders 
receiving baricitinib 4-mg will remain on baricitinib 4-mg.

Responders and Partial Responders receiving placebo, baricitinib 1-mg, 2-mg, or 4-mg at the completion of 
the originating study will remain on their assigned treatment.  If a patient has an IGA ≥3 during treatment 
period 1, then interactive web-response system will assign the following treatments:  placebo and 
baricitinib 1-mg will be rerandomized in a blinded fashion 1:1 to either baricitinib 2-mg or baricitinib 
4-mg; baricitinib 2-mg and 4-mg will remain on the same dose.
Treatment Period 2:  Week 52 (Visit 8) through Week 200 (Visit 22):
At Week 52/Visit 8:  All patients will be assessed for eligibility for the randomized withdrawal and 
downtitration substudy.

Patients with an IGA 0, 1, or 2 at Week 52 who were assigned to baricitinib 4-mg or 2-mg upon enrollment 
to JAHN, who are currently receiving investigational product (IP), and who have not used a high-potency
TCS for the last 14 days will be enrolled into the substudy.  Patients receiving baricitinib 4-mg will be 
rerandomized 1:1:1 to either placebo, baricitinib 2-mg, or baricitinib 4-mg. Patients receiving baricitinib 
2-mg will be rerandomized 1:1:1 to either placebo, baricitinib 1-mg, or baricitinib 2-mg.  If a patient has an 
IGA ≥3 during this treatment period, they will be retreated with their presubstudy baricitinib dose.

All other patients are not eligible for the randomized withdrawal and downtitration substudy, and will
continue on their assigned treatment.
Post-Treatment Follow-Up Period: This period spans from the last treatment visit at Week 200/Visit 22, or early 
termination visit to approximately 28 days following the last dose of IP.
Number of patients:
Based on the above-mentioned originating studies, Study JAHN will enroll approximately 1425 patients.

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Statistical Analysis:
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the modified
intent-to-treat population and safety analyses will be conducted on the safety population.
Primary and secondary discrete efficacy variables will be descriptively summarized by treatment group in terms of 
frequencies and percentages.  Treatment comparisons of discrete efficacy variables between treatment groups may
be made using a logistic regression analysis with disease severity and treatment group in the model. The 
percentages, difference in percentages, and 95% confidence interval (CI) of the difference in percentages would then
be reported. All patients who discontinue the study or the study treatment at any time for any reason or are rescued 
will be defined as nonresponders for the nonresponder imputation analysis for categorical variables after 
discontinuation or rescue and onward.  
Continuous efficacy variables will be descriptively summarized by treatment group in terms of number of patients, 
mean, standard deviation, median, minimum, and maximum. Treatment comparisons of continuous efficacy and 
health outcome variables may be made using a restricted maximum likelihood-based mixed model for repeated 
measures.  The model will include treatment, baseline severity, visit, and treatment-by-visit-interaction as fixed 
categorical effects and baseline score and baseline score-by-visit-interaction as fixed continuous effects. An 
unstructured (co)variance structure will be used to model the between- and within-patient errors. Type III sums of 
squares for the least squares means (LSM) will be used for the statistical comparison; 95% CI will also be reported.
Treatment comparisons of continuous efficacy and health outcome variables may also be made using analysis of 
covariance (ANCOVA) with disease severity, treatment group, and baseline value in the model.  Type III tests for 
LSM may be used for statistical comparison between treatment groups.  The LSM difference, standard error, 
p-value, and 95% CI may also be reported.
All safety data will be descriptively summarized by treatment group and treatment period.  For categorical events, 
Fisher exact test may be used to perform comparisons between each baricitinib dose and the placebo group. Fisher 
exact test may also be used for all 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 ANCOVA with treatment and baseline value in the model.

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2. Schedule of Activities
Table JAHN.1.
I4V-MC-JAHN Schedule of Activities
Treatment Period 1
Treatment Period 2
Screening 
and 
Baseline 
Period
PTFU 
Period
Visit number
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/
ETs
801b
Weeks from entry 
into JAHN
0
4
8
16
24
36
48
52
56
60
64
68
76
84
92
104
120
136
152
168
184
200
204
Visit tolerance 
interval (days) from 
entry into JAHN
0 to 56 from 
last visit of 
originating 
studyc
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±7
±7
±7
±7
±7
±7
28 ± 4 
after 
last 
dose
Procedures
Inclusion and 
exclusion criteria 
review
Xd
Informed consent
Xe
Abbreviated 
demographics
X
Clinical Assessments
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BP and 
pulse)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed 
physical examinationf
X
X
X
X
X
X
X
X
X
X
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
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
X
X
X
X
ePRO (patient diary) 
dispensed
X
X
X
X
Xg
Xg
Xg
Xg
ePRO (patient diary) 
returned
X
X
X
X
X
Xg
Xg
Xg
Xg
Xh
Rerandomizationi, j
X
X
IWRS
Xj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP dispensedj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP returned and 
compliance assessed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense TCS 
(as needed)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

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Treatment Period 1
Treatment Period 2
Screening 
and 
Baseline 
Period
PTFU 
Period
Visit number
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/
ETs
801b
Weeks from entry 
into JAHN
0
4
8
16
24
36
48
52
56
60
64
68
76
84
92
104
120
136
152
168
184
200
204
Visit tolerance 
interval (days) from 
entry into JAHN
0 to 56 from 
last visit of 
originating 
studyc
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±7
±7
±7
±7
±7
±7
28 ± 4 
after 
last 
dose
Weigh (tube with cap) 
and record returned 
TCS (as needed)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
Physician-Assessed Efficacy Measures
IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Health Outcomes Measures and Other Questionnairesk
POEM
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
WPAI-AD
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
EQ-5D-5L
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
Itch NRS
X
X
X
X
X
X
X
X
X
X
Xh
Skin Pain NRS
X
X
X
X
X
X
X
X
X
X
Xh
ADSS
X
X
X
X
X
X
X
X
X
X
Xh
PGI-S-AD
X
X
X
X
X
X
X
X
X
X
Xh
HADS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
C-SSRSl and 
Self-Harm 
Supplement Form 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up 
Formm
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Clinical chemistryn
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Lipids (fasting)p
Xo
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
Xo
X
X
X
X
X
X
X
X
Xs
Xt
HBV DNAq
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancyr
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAHN(c) Clinical Protocol
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Treatment Period 1
Treatment Period 2
Screening 
and 
Baseline 
Period
PTFU 
Period
Visit number
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22/
ETs
801b
Weeks from entry 
into JAHN
0
4
8
16
24
36
48
52
56
60
64
68
76
84
92
104
120
136
152
168
184
200
204
Visit tolerance 
interval (days) from 
entry into JAHN
0 to 56 from 
last visit of 
originating 
studyc
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±7
±7
±7
±7
±7
±7
28 ± 4 
after 
last 
dose
Serum 
immunoglobulin (IgE)
X
X
X
X
Xs
Stored serum and 
plasma samples for 
exploratory analysis
X
X
X
X
Xs
Stored blood for RNA 
analysis
X
X
X
X
Xs
Abbreviations:  ADSS = Atopic Dermatitis Sleep Scale; BP = blood pressure; C-SSRS = Columbia–Suicide Severity Rating Scale; DLQI = Dermatology Life 
Quality Index; EASI = Eczema Area and Severity Index; eGFR = estimated glomerular filtration rate; ePRO = electronic patient-reported outcome (device); 
EQ-5D-5L = the European Quality of Life–5 Dimensions–5 Levels; ET = early termination; HADS = Hospital Anxiety Depression Scale; 
HBcAb = anti-hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBV = hepatitis B virus; IGA = Investigator’s Global Assessment; 
IP = investigational product; IWRS = interactive web-response system; NRS = numeric rating scale; PGI-S-AD = Patient Global Impression of Severity –
Atopic Dermatitis; POEM = Patient-Oriented Eczema Measure; PTFU = post-treatment follow-up; RNA = ribonucleic acid; SCORAD = SCORing Atopic 
Dermatitis; TCS = topical corticosteroids; WPAI-AD = Work Productivity and Activity Impairment Questionnaire – Atopic Dermatitis.
a
For the majority of patients, Visit 1 will also be the last visit of the originating study; thus any assessments/procedures conducted during the final visit of the 
patients’ originating study should not be repeated during their first visit for Study JAHN.
b
Patients who have discontinued IP but remain in the study for more than 28 days without IP can combine their Visit 22/ET with Visit 801 (follow-up visit).
c
For patients not requiring washout, the visit tolerance interval should be 0 days for Visit 1; however, those patients returning after completion of a 4-week 
washout from systemic therapy have a tolerance interval of ≤56 days (8 weeks) from last visit of originating study.  When a patient returns after completion of 
a systemic washout, all Visit 1 procedures should be repeated unless indicated otherwise.
d
For patients requiring a washout from systemic therapy, the review of inclusion and exclusion criteria should be performed at both the last visit of the 
originating study and at the time when the patient returns to complete Visit 1 procedures.
e
For patients requiring a washout from systemic therapy, informed consent should be signed at the last visit of the originating study.
f
If necessary, a symptom-directed physical examination should be performed prior to enrollment to evaluate any condition that would meet the exclusion
criteria.  The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints.
g
Patient diaries are not required for patients known by the investigator to not meet substudy eligibility criteria (IGA score ≥3, patients receiving high-potency
TCS and/or on a study drug interruption at Week 52 [Section 5.1.3.1]).  Thus, patient diaries will not need to be dispensed/returned for visits indicated.
h
Applies only if ET visit occurs while patient has diary.

I4V-MC-JAHN(c) Clinical Protocol
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i
Rerandomization occurs only for nonresponders entering JAHN on placebo, baricitinib 1-mg, or baricitinib 2-mg.
j
For patients requiring a washout from systemic therapy, IWRS registration of Visit 1, dispensing of IP, and rerandomization will not occur until washout is 
complete.
k
The following measures (POEM, DLQI, EQ-5D-5L, WPAI-AD) should be completed prior to any clinical assessments being performed on days when study 
visits occur.
l
Suicidal ideation and behavior subscales excerpt – adapted for the assessment of 11 preferred ideation and behavior categories.
m The Self-Harm Follow-up Form is only required if triggered by the Self-Harm Supplement Form.
n
Clinical chemistry will include the following value calculated from serum creatinine: eGFR (calculated using the CKD-EPI Creatinine 2009 equation).
o
If laboratory examinations have been performed ≤4 weeks from previous study visit, then they do not need to be repeated.
p
Fasting lipid profile; patients should not eat or drink anything except water for 12 hours prior to sample collection.  If a patient attends these visits in a 
nonfasting state, this will not be considered a protocol violation. Unscheduled lipid testing can be performed at the discretion of the investigator.
q
HBV DNA will be performed per the schedule (see Section 9.4.7) in patients who tested positive for HBcAb at screening in the originating study, regardless 
of patient’s HBsAb status.
r
For all women of childbearing potential; if required per local regulations and/or institutional guidelines, pregnancy testing can occur at other times during the 
study treatment period.
s
An ET visit should be conducted if a patient discontinues from the study before Week 200.  Early termination visit activities do not need to be duplicated if 
occurring at the time of a scheduled visit. Weighing of TCS, collection of WPAI-AD, EQ-5D-5L, HADS, urinalysis, serum IgE exploratory storage samples, 
RNA and biomarker samples should only be performed at the ET visit if it occurs at or before Week 104.  
t
For V801, the weighing of TCS, and collection of WPAI-AD, EQ-5D-5L, HADS, and urinalysis should only be performed if it occurs at or before Week 104.
NOTE: Patients completing V16 and planning to sign ICF for amendment (c) can participate as long as they have not completed a V801.

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

I4V-MC-JAHN(c) Clinical Protocol
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3.2.
Study Rationale
The underlying cause of AD is not completely understood.  Loss-of-function mutations in the 
gene for filaggrin (filament aggregating protein), a key protein in terminal differentiation of the
epidermis contributing to barrier function, has been identified as the strongest genetic risk factor
for AD in European populations (Palmer et al. 2006). At a cellular level, AD is characterized by 
excessive T cell activation caused by genetic and environmental factors, leading to significant 
skin infiltration by T cells and dendritic cells.  The cytokine thymic stromal lymphopoietin 
(TSLP) is thought to act as a master switch that triggers the initiation and maintenance of AD 
(Moniaga et al. 2013; Ziegler et al. 2013).  Overexpression of TSLP in keratinocytes, the most 
prevalent cell type in the skin, triggers robust itch-evoked scratching and the development of an 
AD-like skin phenotype in mice (Li et al. 2005). In addition to directly inducing itch by 
activating sensory neurons in the skin, TSLP also enhances maturation and differentiation of 
dendritic cells and naive CD4+ T cells and induces production of Th2-related cytokines involved 
in AD pathogenesis (Wilson et al. 2013; Divekar and Kita 2015).  Thymic stromal lymphopoietin
and other key cytokines involved in AD pathogenesis, such as IL-13, IL-5, IL-22, and IL-31, 
signal through receptors associated with intracellular JAK1/JAK2/tyrosine kinase 2(TYK2) 
signaling (Ziegler et al. 2013; Nomura and Kabashima 2015).
Janus kinases are a family of tyrosine kinases that mediate cytokine receptor signaling through 
phosphorylation and activation of signal transducers and activators of transcription (STAT)
proteins.  There are 4 known JAK family members:  JAK1, JAK2, JAK3, and TYK2 (Clark et al.
2014).  The relative affinity of JAK inhibitors for different members of the JAK kinase family 
allows for differentiation of JAK inhibitors in relation to their enzymatic inhibitory profile.  In 
vitro assays indicate that baricitinib is a selective inhibitor of JAKs with potency and selectivity 
for JAK1/JAK2 and less potency for JAK3 or TYK2 (Fridman et al. 2010).  The balanced 
JAK1/JAK2 inhibitory profile of baricitinib suggests that baricitinib will have greatest 
modulatory effect in cytokines signaling through a JAK1/JAK2 heterodimer intracellularly (or a 
JAK1/JAK2/TYK2, such as IL-6, TSLP, IL-13, or IL-31) (Vaddi and Luchi 2012).
The recently completed Phase 2 study of baricitinib in AD, JAHG, met its primary objective of 
proportion of patients achieving a 50% improvement from baseline in Eczema Area and Severity 
Index (EASI) scores compared to placebo. Baricitinib also showed statistically significant 
improvements for other disease severity analyses as well as multiple different patient-reported 
outcomes (PROs) compared to placebo, further supporting the hypothesis that JAK1/JAK2 
signaling plays a key role in AD pathogenesis.
3.3.
Benefit/Risk Assessment
More information about the known and expected benefits, risks, serious adverse events (SAEs),
and reasonably anticipated adverse events (AEs) of baricitinib are to be found in the 
Investigator’s Brochure (IB).

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4.
Objectives and Endpoints
Table JAHN.2.
Objectives and Endpoints
Objectives
Endpoints
Primary
To estimate the effect of long-term therapy with 
baricitinib on responders and partial responders at 
entry of JAHN.

Proportion of patients with a response of IGA 0 or 1 
assessed at Weeks 16, 36, and 52
Secondary (Weeks 0–52)
Baricitinib Patients at Entry to Study JAHN
To evaluate the effect of increasing or 
maintaining baricitinib dose on clinical measures
and patient-reported outcomes.

Proportion of patients with a response of IGA 0, 1, or 
2 assessed at Weeks 16, 36, and 52

Proportion of patients with a response of IGA 0 or 1 
assessed at Weeks 16, 36, and 52 (nonresponders)

Proportion of patients achieving response of EASI75 
from baseline of originating study assessed at 
Weeks 16, 36, and 52

Proportion of patients with a 4-point improvement 
from baseline of originating study in Itch NRS at 
16 weeks
Placebo Nonresponders at Entry to 
Study JAHN
To evaluate the effect of starting baricitinib 2-mg 
versus 4-mg on clinical measures and 
patient-reported outcomes.

Proportion of patients with a response of IGA 0, 1, or 
2 assessed at Weeks 4, 16, 24, 52

Proportion of patients with a response of IGA 0 or 1 
assessed at Weeks 4, 16, 24, 52

Proportion of patients achieving response of EASI75 
from baseline of originating study assessed at 
Weeks 4, 16, 24, 52

Proportion of patients with a 4-point improvement 
from baseline of originating study in Itch NRS at 
16 weeks
Secondary (Weeks 52–104)
All Patients Entering the Substudy
To evaluate the change in clinical response after 
treatment withdrawal or downtitration.
Patients Entering the Substudy with IGA 0 or 
1
To evaluate the change in clinical response after 
treatment withdrawal or downtitration.

Proportion of patients with a response of IGA 0, 1, or 
2 assessed at 16 weeks after rerandomization
(Week 68) and Week 104

Proportion of patients with a response of IGA 0 or 1 
assessed at 16 weeks after rerandomization (Week 68)
and Week 104

Proportion of patients with a response of EASI75 
from baseline of originating study assessed at 
16 weeks after rerandomization (Week 68) and 
Week 104

Time to retreatment (time to IGA ≥3)
Patients Retreated during Substudy
To evaluate the ability to recapture efficacy based 
on clinical measures after experiencing a loss of 
treatment benefit:

Proportion of patients with a response of IGA 0, 1, or 
2 within 16 weeks of retreatment

Proportion of patients with a response of IGA 0 or 1 
within 16 weeks of retreatment

Proportion of patients with a response of EASI75 
from baseline of originating study within 16 weeks of 
retreatment

I4V-MC-JAHN(c) Clinical Protocol
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LY3009104
Objectives and Endpoints
Objectives
Endpoints
Patients Not Entered into the Substudy
To evaluate the effect of maintaining baricitinib 
dose on clinical measures.

Proportion of patients with a response of IGA 0, 1, or 
2 assessed at Week 104

Proportion of patients with a response of IGA 0 or 1 
assessed at Week 104

Proportion of patients with a response of EASI75 
from baseline of originating study assessed at 
Week 104
Exploratory objectives may include evaluating the response to baricitinib treatment regimens on clinical measures 
and patient-reported outcomes.  These endpoints may include dichotomous endpoints or change from baseline for 
the following measures:  IGA, EASI, SCORAD, POEM, DLQI, WPAI-AD, EQ-5D-5L, Itch NRS, ADSS Item 2 
score, Skin Pain NRS, PGI-S-AD.  Patients continuing on placebo as responders will be assessed during the 
long-term extension for relevant efficacy endpoints.  Assessments of efficacy may be performed beyond Week 104 
up to Week 200.  The timing of the data lock(s) for the analysis of the efficacy data from the sub-study will be 
determined by the retreatment rates (see Section 10.3.7).  
Abbreviations:  ADSS = Atopic Dermatitis Sleep Scale; DLQI = Dermatology Life Quality Index; EASI = Eczema 
Area and Severity Index; EQ-5D-5L = the European Quality of Life–5 Dimensions–5 Levels; 
IGA = Investigator’s Global Assessment; NRS = numeric rating scale; PGI-S-AD = Patient Global Impression of 
Severity – Atopic Dermatitis; POEM = Patient-Oriented Eczema Measure; SCORAD = SCORing Atopic 
Dermatitis; TCS = topical corticosteroids; WPAI-AD = Work Productivity and Activity Impairment
Questionnaire – Atopic Dermatitis.

I4V-MC-JAHN(c) Clinical Protocol
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5.
Study Design
5.1.
Overall Design
Study I4V-MC-JAHN (JAHN) is a Phase 3, multicenter, double-blind study to evaluate the 
long-term safety and efficacy of daily baricitinib 1-mg, 2-mg, and 4-mg in patients with AD for 
approximately 4 years.  The study will consist of 3 study periods and 1 substudy:  randomized 
treatment withdrawal and downtitration.  Patients entering Study JAHN will be classified as 
“Responders and Partial Responders” or “Nonresponders.”  Figure JAHN.1 illustrates the study 
design.  The full visit schedule is outlined in the Study Schedule of Activities (Section 2).  
Patients who completed originating Studies I4V-MC-JAHL (JAHL) and I4V-MC-JAHM
(JAHM) may be eligible for enrollment into Study JAHN; there may also be additional studies 
developed that will be eligible to enroll patients directly into Study JAHN.
Patients completing Studies JAHL and JAHM will have had approximately 16 weeks of 
treatment with investigational product (IP) (baricitinib or placebo) and will enter Study JAHN at 
Visit 1; the final visit of Study JAHL or JAHM will be the first visit of Study JAHN.  Patients 
will have been using emollients daily in their originating study and this will continue during 
Study JAHN participation. If oral systemic AD treatments were administered for rescue in the 
originating study, then a minimum washout of 4 weeks is required prior to study drug initiation 
in Study JAHN (Visit 1). Daily diary collection will continue through the first 4 months of 
treatment in JAHN and then collection will resume at Week 48 for an additional 5 months to 
capture PROs prior to and during the withdrawal and downtitration substudy (except for patients 
known not to be in the substudy [Section 5.1.3.1]).

I4V-MC-JAHN(c) Clinical Protocol
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Abbreviations:  BARI = baricitinib; ET = early termination; IGA = Investigator’s Global Assessment; TCS = topical corticosteroids; 
V = visit.a Background TCS may be initiated or reinitiated at any time during the study, following the guidelines in Section 7.7.1 and 
will be provided as part of rescue or retreatment any time a patient’s IGA score becomes ≥3 as described in Sections 5.1.2.1 and 
5.1.3.1.
b
Eligible patients will be rerandomized in the withdrawal and downtitration substudy as described in Section 5.1.3.1.  Patients 
who do not enroll in the substudy will remain on their treatment as described in Section 5.1.3.2.
c
Patients enrolled in the substudy will automatically be retreated if their IGA score becomes ≥3 as described in Section 5.1.3.1.
d
Rescue is available as described in Section 5.1.2.1.
Figure JAHN.1.
Illustration of study design for clinical Protocol I4V-MC-JAHN.

I4V-MC-JAHN(c) Clinical Protocol
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LY3009104
5.1.1. Screening and Baseline Period
Screening should occur during the last visit of the originating study. However, in particular 
circumstances, the screening period may be extended:

if the patient received oral systemic AD treatment as rescue therapy during the 
originating study and needs additional time to complete the required 4-week washout 
period.  In this situation, patients will need to return in order to complete additional 
Visit 1 procedures required at the end of the washout period. (See the Study Schedule of 
Activities [Section 2].) For these patients, the screening period should not exceed 
8 weeks following the completion of the Week 16 visit in the originating study unless 
approval is obtained from the sponsor.

it may be permissible for screening to occur after the last visit of the originating study if 
needed, upon approval from the sponsor.
Study eligibility for each patient will be reviewed based on all enrollment criteria (Section 6).  
Patients who meet all criteria will have treatment allocated by interactive web-response system 
(IWRS) and begin their treatment period at Visit 1.  Doses include placebo, baricitinib 1-mg, 
baricitinib 2-mg, and baricitinib 4-mg.  Patients with renal impairment at screening (Visit 1) of 
the originating study will not receive doses higher than 2-mg baricitinib.  Available treatment 
assignments will depend on patients’ responder status at enrollment.  An IWRS will determine 
patients’ responder status based on the following criteria:

Responders (Investigator’s Global Assessment [IGA] of 0 or 1) and Partial 
Responders (IGA of 2):  Patients entering Study JAHN who have an IGA score of 0, 1, 
or 2 AND were not rescued in the originating study.

Nonresponders: any patient who does not meet the “Responder and Partial Responder”
definition.
5.1.2. Treatment Period 1:  0 to 52 Weeks
5.1.2.1.
Responders and Partial Responders
Treatment for responders and partial responders is diagramed in Figure JAHN.1.  Patients 
entering Study JAHN as a responder or partial responder will remain on their original, 
randomized treatment assignment:  placebo, baricitinib 1-mg, baricitinib 2-mg, or baricitinib 
4-mg.  These patients did not require rescue during their originating study; thus, they will 
continue with baricitinib monotherapy unless topical corticosteroids (TCS) are deemed 
necessary.  Topical corticosteroids can be initiated any time during treatment to control 
worsening and unacceptable symptoms of AD.  For management of TCS, follow the guidelines 
in Section 7.7.1.
If worsening of symptoms results in an IGA ≥3, patients not currently receiving TCS will be 
provided TCS and automatically rescued as follows:

patients receiving baricitinib 1-mg or placebo will be rerandomized 1:1 to baricitinib 
2-mg or baricitinib 4-mg.

patients receiving baricitinib 2-mg or 4-mg will continue their same baricitinib dose.

I4V-MC-JAHN(c) Clinical Protocol
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LY3009104
This option is only available once for each patient and will be assigned by IWRS; investigators 
will remain blinded to treatment assignments.  Once this has occurred, the investigator will know 
that a patient is on the highest dose of baricitinib that they will receive in the study; therefore, if 
AD symptoms remain unacceptable then discontinuation should be considered.  Although 
patients receiving baricitinib 2-mg and 4-mg will remain on the same dose during rescue, this is 
done to maintain the blind and assess the effect of long-term therapy with these doses.
At Week 52, patients will be assessed for eligibility for the substudy.
5.1.2.2.
Nonresponders
Treatment for nonresponders is diagramed in Figure JAHN.1.  Patients entering as a 
nonresponder on placebo, baricitinib 1-mg, or baricitinib 2-mg will be rerandomized 1:1 to either 
baricitinib 2-mg or baricitinib 4-mg.  Patients entering Study JAHN as a nonresponder on 
baricitinib 4-mg will remain on baricitinib 4-mg.  Patients classified as nonresponders include all 
patients who were rescued at any time during the originating study or have an IGA ≥3 at baseline 
of JAHN.  For patients with unacceptable symptoms, background TCS is permitted upon 
enrollment.  Higher potency TCS can be used as needed and patients who had discontinued TCS 
can restart as necessary according to the guidelines in Section 7.7.1.  There are no additional 
treatment modification options for nonresponders after enrollment into JAHN.  Patients are on 
the highest dose of baricitinib that they will receive in the study; therefore, if AD symptoms are 
unacceptable then discontinuation should be considered.
At Week 52, patients will be assessed for eligibility for the substudy.
5.1.3. Treatment Period 2:  52 to 200 Weeks
5.1.3.1.
Substudy at Week 52:  Randomized Withdrawal and Downtitration
Eligibility
At Week 52, all patients will be evaluated for substudy eligibility.  To be eligible, a patient must 
meet all of the following criteria:

IGA 0, 1, or 2 at Week 52

has not used high-potency TCS in the last 14 days (potency classification in Appendix 6)

does not currently have study drug interrupted

at entry to JAHN was assigned to baricitinib 2-mg or 4-mg (assessed by IWRS)
Investigators will be aware of the patients not meeting the first 3 criteria, and thus not included in 
the substudy; however, there will be some patients for which substudy participation is not known
based on the originally assigned dose.  As such, IGA ≥3 is the criteria for both retreatment (in 
substudy) and rescue (not in substudy) for these patients to ensure all patients are treated 
similarly and the blind to treatment group is preserved.  All patients who meet the first 3 criteria 
will continue to follow substudy procedures to maintain the blind.

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Treatment
Treatment in the substudy is diagramed in Figure JAHN.1.  Patients entering the substudy on 
baricitinib 4-mg will be rerandomized 1:1:1 to either placebo, baricitinib 2-mg, or baricitinib 
4-mg.  Patients entering the substudy on baricitinib 2-mg will be rerandomized to either placebo, 
baricitinib 1-mg, or baricitinib 2-mg.  Topical corticosteroids can be continued or initiated to 
control worsening and unacceptable symptoms of AD any time during treatment.  For 
management of TCS, follow the guidelines in Section 7.7.1.
Retreatment
During the substudy, if worsening of AD symptoms occurs with an IGA ≥3, the patient will be 
retreated with their original baricitinib dose and will be provided TCS.  An unscheduled visit 
may be needed in order to assess worsening and perform clinical safety and efficacy assessments 
immediately before retreatment.
5.1.3.2.
Patients Not Entered into the Substudy
All patients not entered into the substudy will continue on their current treatment. Topical 
corticosteroids can be initiated any time during treatment to control worsening and unacceptable 
symptoms of AD.  For management of TCS, follow the guidelines in Section 7.7.1.  If worsening 
of symptoms results in an IGA ≥3, patients not currently receiving TCS will be provided TCS 
and automatically rescued as follows:

Patients entering Study JAHN as responders or partial responders who have not 
previously been rescued during Treatment Period 1 (0 to 52 weeks) are eligible for 
rescue:
o
patients receiving baricitinib 1-mg or placebo will be rerandomized 1:1 to 
baricitinib 2-mg or baricitinib 4-mg.
o
patients receiving baricitinib 2-mg or 4-mg will continue their same baricitinib 
dose.

Patients entering Study JAHN as nonresponders and patients already rescued during 
Treatment Period 1 (0 to 52 weeks) are not eligible for a second rescue and will continue 
on the same dose.
5.1.4. Post-treatment Follow-up Period
Patients who complete the study through Visit 22 (Week 200) will have a post-treatment 
follow-up visit (Visit 801) approximately 28 days after the last dose of IP.  
Patients who discontinue early from the study must have an early termination visit (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; however, a separate follow-up visit (Visit 801) is not required.

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5.2.
Number of Participants
Approximately 1760 patients may be enrolled in Study JAHN, either from originating studies 
(such as Study JAHL, Study JAHM, or Study JAIY) or future studies or addenda.  It is estimated 
that there will be approximately 600 patients enrolled into the randomized treatment withdrawal 
and downtitration substudy.
5.3.
End of Study Definition
End of the trial is the date of the last visit or last scheduled procedure as shown in the Schedule 
of Activities (Section 2) for the last patient.
5.4.
Scientific Rationale for Study Design
Atopic dermatitis is a chronic, relapsing inflammatory skin disorder (Bieber 2010).  Although
several therapies are available to patients for the treatment of flares, there are very limited 
options for long-term management. Most patients rely on chronic use of emollients and 
intermittent use of TCS or topical calcineurin inhibitors (TCNIs) to regulate skin inflammation in 
response to flares.  In patients with moderate to severe disease, long-term disease control is not 
always achieved. In order to address this important medical need for a safe and effective 
long-term therapy, this study will allow for a longer treatment period (up to 4 years).
To adequately assess the long-term effect of specific baricitinib doses, there are instances where 
patients will remain on their same dose during episodes of worsening disease.  However, use of 
topical treatments (as outlined in Section 7.7.1) is available during Study JAHN.
Treatment withdrawal or dose downtitration for patients with sustained response to therapy are 
strategies that may be used in the clinical setting.  Study JAHN will evaluate the effect of 
stopping or decreasing the dose of baricitinib in the context of a randomized treatment
withdrawal and downtitration substudy starting at Week 52.  This timing will allow adequate 
duration on a stable dose of baricitinib to assess the benefit/risk profile of the dose regimens.  It 
is anticipated that the effects of downtitration and withdrawal will be more reliably assessed in 
those continuously treated with the 2-mg or 4-mg doses; thus, those being treated with 1-mg are 
not eligible for the substudy.
5.5.
Justification for Dose
The doses proposed for AD Phase 3 studies are baricitinib 1-mg, 2-mg, and 4-mg.  These doses 
were chosen primarily based on the recently completed Phase 2 AD study, JAHG, and are 
additionally supported by pharmacokinetic (PK), safety, and efficacy data for baricitinib in 
Phase 2 and Phase 3 RA studies and a Phase 2 psoriasis study.
In the Phase 2 Study JAHG, both the 2-mg and 4-mg doses showed benefit on the primary and 
major secondary endpoints (EASI, IGA, SCORing Atopic Dermatitis [SCORAD], 
Patient-Oriented Eczema Measure [POEM], and the Dermatology Life Quality Index [DLQI]) as 
compared to placebo, and both doses had an acceptable safety profile at Week 16.  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 2-mg dose particularly in the 

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subgroup of patients with baseline EASI scores ≥16.  The 4-mg dose resulted in statistically 
significant improvement in these endpoints at Week 4 and this level of response was maintained 
through Week 16.  A similar trend between the baricitinib 4-mg and 2-mg doses was observed in 
patients with RA.  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.  
Thus, based on available data, 3 doses will be included in Phase 3, including a 1-mg dose, to 
cover the range of exposures where clinical responses could be anticipated.
5.5.1. Dose Adjustment for Renal Impairment
Patients who received a dose adjustment due to renal impairment in their originating study will 
continue to receive a renal dose adjustment in Study JAHN.
Baricitinib exposure increases with decreased renal function (Study I4V-MC-JADL).  Based on 
PK simulations of baricitinib exposures for the mild and moderate categories of renal function 
(stratified as estimated glomerular filtration rate [eGFR] 60 to <90 mL/min/1.73 m2 and eGFR 
30 to <60 mL/min/1.73 m2, respectively), dose adjustment is not required for patients with eGFR 
≥60 mL/min/1.73 m2.
During Study JAHN, patients with eGFR <60 mL/min/1.73 m2 who are randomized to the 4-mg 
dose will receive a dose of 2-mg, ensuring that their exposures would not exceed those of the 
4-mg dose in patients with eGFR ≥60 mL/min/1.73 m2.  For patients randomized to the 2-mg or 
1-mg dose, there is no dose correction based on renal function.  See Section 8.1.1 for eGFR 
thresholds that trigger interruption of IP.
The procedure of dose adjustment based on renal function (eGFR) during the study is detailed in 
Section 7.2.2.

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6.
Study Population
The study population will comprise patients diagnosed with AD who have completed an eligible 
originating study. Study investigator(s) will review patient records and screening test results to 
determine that the patient meets all inclusion and exclusion criteria to qualify for participation in 
the study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet the following criteria:
[1]
Have completed the final active treatment visit for an originating study (i.e., 
Visit 8, Week 16 of Studies JAHL or JAHM) eligible to enroll patients 
directly into Study JAHN.
[2]
Are able to read, understand, and give documented (electronic or paper 
signature) informed consent.
[3]
Are male or nonpregnant, nonbreastfeeding female patients, except
a.
Male patients must agree to use 2 forms of birth control (one must be 
highly effective, see below) while engaging in sexual intercourse with 
female partners of childbearing potential while enrolled in the study and 
for at least 4 weeks following the last dose of IP.
b.
Female patients of childbearing potential must agree to use 2 forms of 
birth control when engaging in sexual intercourse with a male partner 
while enrolled in the study and for at least 4 weeks following the last 
dose of IP.
The following birth control methods are considered acceptable (the patient should choose 
2 methods to be used with her male partner, and 1 must be highly effective):
o
Highly effective birth control methods: oral, injectable, or implanted 
hormonal contraceptives (combined estrogen/progesterone or 
progesterone only, associated with inhibition of ovulation); 
intrauterine device or intrauterine system (e.g., progestin-releasing 
coil); or vasectomized male (with appropriate post-vasectomy 
documentation of the absence of sperm in the ejaculate)
o
Effective birth control methods: condom with a spermicidal foam, 
gel, film, cream, or suppository; occlusive cap (diaphragm or 
cervical/vault caps) with a spermicidal foam, gel, film, cream, or 
suppository; or oral hormonal contraceptives
Note: When local guidelines concerning highly effective or effective methods of birth 
control differ from the above, the local guidelines must be followed.

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c.
Females of nonchildbearing potential are not required to use birth 
control and they are defined as:
o
women ≥60 years of age or women who are congenitally sterile, or
o
women ≥40 and <60 years of age who have had a cessation of 
menses for ≥12 months and a follicle-stimulating hormone test from
baseline in originating study, confirming nonchildbearing potential 
(≥40 mIU/mL or ≥40 IU/L), or
o
women who are surgically sterile (i.e., have had a hysterectomy or 
bilateral oophorectomy or tubal ligation).
6.2.
Exclusion Criteria
Patients will be excluded from the study if they meet any of the following criteria:
[4]
Are currently enrolled in any other clinical trial involving an IP or any other 
type of medical research judged not to be scientifically or medically 
compatible with this study.
[5]
Have significant uncontrolled cerebro-cardiovascular (e.g., myocardial 
infarction [MI], unstable angina, unstable arterial hypertension, severe heart 
failure, or cerebrovascular accident), respiratory, hepatic, renal, 
gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or 
abnormal laboratory values that developed during a previous baricitinib study 
that, in the opinion of the investigator, pose an unacceptable risk to the patient 
if IP continues to be administered.
[6]
Have a known hypersensitivity to baricitinib or any component of this IP.
[7]
Had IP permanently discontinued at any time during a previous baricitinib 
study, except for patients who had IP discontinued during originating study 
due to rescue with an oral systemic AD therapy (e.g., corticosteroid, 
cyclosporine, methotrexate)
[8]
Had temporary IP interruption at the final study visit of a previous baricitinib 
study and, in the opinion of the investigator, this poses an unacceptable risk 
for the patient’s participation in the study.
[9]
Have any other condition that, in the opinion of the investigator, renders the 
patient unable to understand the nature, scope, and possible consequences of 
the study or precludes the patient from following and completing the protocol.
[10] Are unwilling or unable to comply with the use of a data collection device to 
directly record data from the subject.
6.3.
Lifestyle Restrictions
Not applicable.

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6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened.

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7. Treatments
7.1.
Treatments Administered
Patients in this long-term extension study will receive either baricitinib 1-mg, baricitinib 2-mg, 
baricitinib 4-mg, or placebo administered orally once a day. Patients with renal impairment who 
received a baricitinib dose of 2-mg daily in the originating study will continue to receive a 2-mg 
daily dose of baricitinib in Study JAHN.  Patients with renal impairment randomized to 
baricitinib 4-mg in JAHN will receive baricitinib 2-mg; patients with renal impairment 
randomized to baricitinib 2-mg or 1-mg in Study JAHN will not have their dose modified.  
Table JAHN.3 shows the treatment regimens.
Table JAHN.3.
Treatment Regimens
Assigned Treatment
IP Supplied in JAHN
Dose
Baricitinib 4-mg QDa
Baricitinib 4-mg tablets
Placebo to match 2-mg tablets
Placebo to match 1-mg tablets
3 tablets per day
Baricitinib 2-mg QD
Baricitinib 2-mg tablets
Placebo to match 4-mg tablets
Placebo to match 1-mg tablets
3 tablets per day
Baricitinib 1-mg QD
Baricitinib 1-mg tablets
Placebo to match 4-mg tablets
Placebo to match 2-mg tablets
3 tablets per day
Placebo QD
Placebo to match 4-mg tablets
Placebo to match 2-mg tablets
Placebo to match 1-mg tablets
3 tablets per day
Abbreviations:  eGFR = estimated glomerular filtration rate; IP = investigational product; QD = once daily.
a
The maximum baricitinib dose for patients with renal impairment, defined as eGFR <60 mL/min/1.73 m2, will be 
2-mg QD.
The investigator or his/her designee is responsible for the following:

explaining the correct use of the investigational agent(s) to the patient

verifying that instructions are followed properly

maintaining accurate records of 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 medications are to be 
destroyed by the site, as allowed by local law.
Patients will be instructed to take 3 tablets daily: 1 tablet matching appearance of baricitinib 
4-mg, 1 tablet matching appearance of baricitinib 2-mg, and 1 tablet matching appearance of 
baricitinib 1-mg.  All 3 tablets should be taken together, at the same time each day.

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7.1.1. Packaging and Labeling
The sponsor (or its designee) will provide the following IPs:

tablets containing 4-mg baricitinib

tablets containing 2-mg baricitinib

tablets containing 1-mg baricitinib

placebo tablets to match baricitinib 4-mg, 2-mg, and 1-mg tablets.
Packaging for each dose will include 3 tablets per day.  Each tablet has a distinctive shape and 
color, 4-mg versus 2-mg versus 1-mg, and each tablet strength has a matching placebo.  Each 
active dose package will contain the appropriate active tablet strength, and corresponding 
placebo tablets for the other strengths, as noted in Table JAHN.3.
Investigational product tablets will be provided in cartons containing 4 blister packs.
Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.2.
Method of Treatment Assignment
At entry into JAHN, patients who meet all criteria for enrollment will be randomized or assigned 
treatment by a computer-generated random sequence using an IWRS.  Patients originally 
assigned to placebo, 1-mg baricitinib or 2-mg baricitinib in studies JAHL or JAHM and 
classified as nonresponders will be randomized in a 1:1 ratio to 2-mg baricitinib or 4-mg 
baricitinib and will be stratified by disease severity at baseline of JAHN (IGA 0, 1, 2 versus 
IGA 3 versus IGA 4).  All other patients will be assigned to treatment in JAHN matching their 
prior assignment from JAHL or JAHM.  Assignment to treatment groups will be determined by a 
computer-generated random sequence using an IWRS.
At Week 52, patients eligible for the withdrawal and downtitration substudy will be assigned to 
treatment by a computer-generated random sequence using an IWRS.  Rerandomization will 
follow a 1:1:1 ratio allocation and will be stratified by disease severity (IGA 0, 1 versus IGA 2).
The IWRS will be used to assign blister packs, each containing double-blind IP tablets, to each 
patient, starting at Visit 1 (Week 0), and at each visit up to and including Visit 21 (Week 184).  
Site personnel will confirm that they have located the correct blister packs by entering a 
confirmation number found on the blister packs into the IWRS.
7.2.1. Selection and Timing of Doses
The IP (3 tablets from blister pack) should be taken once daily without regard to food and, if 
possible, at approximately the same time every day, usually at the start of the patient’s day, to aid 
patient compliance.
7.2.2. Dose Adjustment for Renal Impairment
The rationale of dose adjustment for patients with documented renal impairment (defined as 
screening in the originator study eGFR ≥40 to <60 mL/min/1.73 m2) is detailed in Section 5.5.1.

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The dose adjustment for renal impairment will be managed by IWRS to ensure maintenance of 
the treatment blind.  Patients who received dose adjustment for renal impairment in their 
originator study will continue to receive dose adjustment in JAHN.
Patients with documented renal impairment (defined as screening in the originator study eGFR 
≥40 to <60 mL/min/1.73 m2), who are randomized to the 4-mg active treatment arm will receive
a dose of 2-mg by the IWRS. For patients randomized to the 2–mg dose or 1–mg dose, there 
will be no dose adjustment based on renal function.
No dose adjustment will be made for patients with screening eGFR ≥60 mL/min/1.73 m2 in the 
originator study.  These patients who are randomized to active treatment will receive their 
assigned dose, either baricitinib 4–mg, 2–mg, or 1–mg, respectively.
During the study, for patients with documented renal impairment when the subsequent eGFR 
falls <30 mL/min/1.73 m2, IP will be withheld until their eGFR becomes ≥40 mL/min/1.73 m2, 
whereupon the IP dosing may resume.  For patients with screening eGFR ≥60 mL/min/1.73 m2,
when the subsequent eGFR falls to <40 mL/min/1.73 m2, IP will be withheld until their eGFR 
becomes ≥50 mL/min/1.73 m2, whereupon the IP dosing may resume (see Section 8.1.1).
7.3.
Blinding
This is a double-blind study. To preserve the blinding of the study, a minimum number of Lilly 
personnel will see the randomization table and treatment assignments before the study is 
complete.  All study assessments will be performed by study personnel who are blinded to the 
patient’s treatment group.  Except in clinical circumstances where unblinding is required, the 
patients, investigators, Lilly study team, and any personnel interacting directly with patients or 
investigative sites will remain blinded to baricitinib and placebo assignment until after 
completion of the double-blinded treatment period.  It is expected that the need for unblinding a 
patient’s treatment prior to completion of the double-blinded treatment period will be extremely 
rare.  Every effort should be made to preserve the blind unless there is a compelling reason that
knowledge of the specific treatment would alter the medical care of the patient.  In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
patient’s treatment assignment is warranted for medical management of the event.  Patient safety 
must always be the first consideration in making such a determination.  If a patient’s treatment 
assignment is unblinded, Lilly must be notified immediately.  If the investigator decides that 
unblinding is warranted, it is the responsibility of the investigator to promptly document the 
decision and rationale and notify Lilly as soon as possible.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment.  All 
unblinding events are recorded and reported by the IWRS.  If an investigator, site personnel 
performing assessments, or the patient is unblinded, the patient must be discontinued from the 
study.  In cases where there are ethical reasons to have the patient remain in the study, the 
investigator must obtain specific approval from a Lilly clinical research physician for the patient 
to continue in the study.

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The processes to maintain blinding during the interim analysis conducted by the Data Monitoring 
Committee (DMC) are described in Section 10.3.7.
7.4.
Dosage Modification
Not applicable.
7.5.
Preparation/Handling/Storage/Accountability
All IPs (used and partially used) will be returned to the sponsor or destroyed at site level with the 
sponsor’s written approval.  In some cases, sites may destroy the material if, during the 
investigative site selection, the evaluator has verified and documented that the site has 
appropriate facilities and written procedures to dispose of clinical trial materials.
Follow storage and handling instructions on the IP packaging.
7.6.
Treatment Compliance
Patient compliance with IP will be assessed at Visit 2 through Visit 22 and at Early Termination 
during the treatment period by counting returned tablets.
A patient will be considered significantly noncompliant if he or she misses more than 20% of the 
prescribed doses of IP during the study, unless the patient’s IP is withheld by the investigator for 
safety reasons.  Similarly, a patient will be considered significantly noncompliant if he or she is 
judged by the investigator to have intentionally or repeatedly taken 20% more than the 
prescribed amount of medication during the study.
Patients will be counseled by study staff on the importance of taking the IP as prescribed, as 
appropriate.
Patients’ compliance will be further defined in the statistical analysis plan (SAP).
7.7.
Concomitant Therapy
All concomitant medications, whether prescription or over-the-counter, must be recorded on the 
Concomitant Medication electronic case report form (eCRF).  Patients will be instructed to 
consult the investigator or other appropriate study personnel at the site before taking any new 
medications or supplements during the study.
7.7.1. Topical Corticosteroids and Other Topical Treatments
Prior to use of TCS, it is recommended that increased frequency of emollient use is attempted at 
least twice a day in an effort to control symptoms.  If symptoms are still not controlled, and 
topical treatments other than emollients are needed, then the investigator should start with 
low-to-medium-potency TCS options.
Choice of Topical Treatment

Triamcinolone cream 0.1% and/or hydrocortisone 2.5% ointment.  Where possible both 
of these treatments will be supplied by the sponsor during the first 2 years of the 
treatment period (dispensed at Visits 1-15), and use should be recorded via weight of 

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returned tube as indicated in the SOA (Section 2).  In the event of these specific TCS 
being unavailable during the first 2 years, an alternate, equivalent-potency TCS may be 
provided by the sponsor. Following Visit 15, patients may independently continue to use 
their TCS of choice as directed by their investigator, as per clinical practice, but these 
will not be provided by the sponsor and weight will not be recorded. 
o
In the event that the sponsor is unable to supply TCS during the first 2 years, 
commercially available triamcinolone 0.1% cream and/or hydrocortisone 2.5% 
ointment may be supplied by the sites. Where providing triamcinolone 0.1% 
cream and/or hydrocortisone 2.5% ointment is not possible, an equivalent-potency 
TCS cream and/or ointment that is in line with local practices can be supplied.  
Refer to Appendix 6 for guidance on potency equivalence. 
o
If the TCS supplied by the sponsor during the first 2 years is not considered 
suitable for an individual patient, an equivalent-potency TCS cream and/or 
ointment that is in line with local practices can be supplied by the sites.  Refer to 
Appendix 6 for guidance on potency equivalence.

Investigators may also select to use TCNIs and/or crisaborole where approved, 
although use of either during the study is neither encouraged nor 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 should not be applied before the patient has 
undergone all study procedures and clinical evaluations in order to allow adequate 
assessment of skin dryness.

Use of any topical therapy will be documented in the CRF.
In patients who do not improve sufficiently with the provided topical therapy after 7 days, a 
higher potency TCS may be used (Appendix 6) and IP may continue.  Higher potency TCS will 
not be supplied centrally by the sponsor.  It is recommended that if a patient reaches “clear” to 
“almost clear” skin while receiving topical therapy, then medium- or high-potency TCS and 
TCNI should be stopped, and low–potency TCS should be used once daily for 7 days then 
stopped.  Following cessation of TCS, if a patient again experiences worsening and unacceptable 
symptoms of AD then TCS can be re-initiated at the discretion of the investigator.
The protocol states that in certain circumstances TCS will be provided; however, the decision to 
dispense TCS is ultimately at the investigator’s discretion.
7.7.2. Other Permitted Medications and Procedures
Treatment with concomitant AD therapies during the study is permitted only as described below.

Daily use of emollients is required as background treatment.  If daily applications
are missed, it will not be considered a protocol violation.
o
Patients should not apply emollients on the day of their study visit prior to the 
procedures to allow adequate assessment of skin dryness.

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
Antihistamines are allowed.

Intra-articular or soft tissue (bursa, tendons, and ligaments) corticosteroid 
injections are allowed.

Intranasal or inhaled steroid use is allowed.

Topical anesthetics and topical and systemic anti-infective medications are 
allowed.

Nonlive seasonal vaccinations and/or emergency vaccination, such as rabies or 
tetanus vaccinations, are allowed.
Any changes of these concomitant medications must be recorded in the Concomitant Therapy of 
Special Interest eCRF.
Treatment with concomitant therapies for other medical conditions such as diabetes and 
hypertension is permitted during the study.
7.7.3. Prohibited Medications and Procedures
Prohibited Medications and Procedures Not Requiring 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.  

phototherapy including PUVA (psoralen and ultraviolet A), ultraviolet B, tanning 
booth, and excimer laser

bleach baths
Prohibited Medications Requiring Temporary Interruption of Investigational Product
The following therapies will not be allowed during the course of the study and, if taken by or 
administered to the patient, temporary interruption of investigational product is required.

live vaccines (including Bacillus Calmette-Guérin [BCG] or herpes zoster)
o
For BCG vaccination, investigational product should be temporarily interrupted 
for 12 weeks
o
For herpes zoster vaccination, investigational product should be temporarily 
interrupted for 4 weeks 

probenecid:  if a patient is inadvertently started on probenecid, IP should be 
temporarily interrupted, and can be resumed after patient has discontinued 
probenecid. If a patient is not able to discontinue probenecid, then IP should be 
permanently discontinued

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
systemic corticosteroids may be used for the treatment of an AE (for example,
worsening of existing condition, such as asthma flare). Investigational product 
may be restarted if systemic corticosteroids were used for a short duration 
(<30 days).  If used for >30 days, sponsor approval to restart investigational 
product is required.  
Prohibited Medications Requiring Permanent Discontinuation of Investigational Product

systemic corticosteroids used for the treatment of AD

any other systemic therapy, investigational or commercial (approved or off-label 
use), used for the treatment of AD except for antihistamines

other JAK inhibitors (e.g., tofacitinib and ruxolitinib)

systemic immunosuppressive/immunomodulatory substances, including, but not 
limited to, cyclosporine, methotrexate, mycophenolate mofetil, interferon-γ, 
azathioprine, or biologic agents
Note:  In the event that these prohibited medications were inadvertently used, agreement and 
documentation to continue investigational product must be sought from sponsor.
7.8.
Treatment after the End of the Study
7.8.1. Continued Access
Baricitinib will not be made available to patients after conclusion of the study.  Patients will be 
referred to their local treatment centers for continued therapy as clinically indicated.

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Temporary Interruption 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 AE considered to be 
related to study treatment, 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 
predefined in this section.
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table JAHN.4, specific guidance is provided for temporarily interrupting treatment and when 
treatment may be restarted.  Retest frequency and timing of follow-up laboratory tests to monitor 
the abnormal finding 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 JAHN.4 may be restarted at the discretion of the investigator.
Table JAHN.4.
Criteria for Temporary Interruption of Investigational Product
Hold IP if the Following Laboratory Test Results or 
Clinical Events Occur:
IP May Be Resumed When:
WBC count <2000 cells/L
(<2.00x103/L or <2.00 GI/L)
WBC count 2500 cells/L
(≥2.50x103/L or ≥2.50 GI/L)
ANC <1000 cells/L
(<1.00x103/L or <1.00 GI/L)
ANC ≥1200 cells/L
(≥1.20x103/L or ≥1.20 GI/L)
Lymphocyte count <500 cells/L
(<0.50x103/L or <0.50 GI/L)
Lymphocyte count 750 cells/L
(≥0.75x103/L or ≥0.75 GI/L)
Platelet count <75,000/L
(<75x103/L or <75 GI/L)
Platelet count 100,000/L
(≥100x103/L or ≥100 GI/L)
eGFR <40 mL/min/1.73 m2 (from serum creatinine) for 
patients with originating study screening eGFR
≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 (from serum creatinine) for 
patients with originating study screening eGFR ≥40 to 
<60 mL/min/1.73 m2
eGFR 40 mL/min/1.73 m2
ALT or AST >5 x ULN
ALT and AST return to <2 x ULN, and IP is not 
considered to be the cause of enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 10 g/dL (≥100.0 g/L)
Symptomatic herpes zoster
All skin lesions have crusted and are resolving
Infection that, in the opinion of the investigator, merits the 
IP being interrupted
Resolution of infection

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Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; WBC = white blood cell.
Although temporary interruption of IP is not a requirement at times of increased potential risk of 
VTE (venous thromboembolic event; e.g., surgery, significant air travel, or other situations 
involving prolonged immobilization), following appropriate VTE prophylaxis guidelines is
recommended to help manage the elevated risk under these circumstances.
For specific guidance on temporary interruption of IP after use of a prohibited medication, please 
refer to Section 7.7.3 (Prohibited Medications and Procedures).
Lastly, IP should be temporarily interrupted for suicidal ideation or any suicide-related behaviors
as assessed by the following patient responses on the Columbia-Suicide Severity Rating Scale 
(C-SSRS):

A “yes” answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without 
Specific Plan) or

A “yes” answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on 
the “Suicidal Ideation” portion of the C-SSRS or

A “yes” answer to any of the suicide-related behaviors (actual attempt, interrupted 
attempt, aborted attempt, preparatory act or behavior) on the “Suicidal Behavior” portion 
of the C-SSRS.
NOTE:  Prior to resumption of IP, it is recommended that the patient be assessed by a 
psychiatrist or appropriately trained professional to assist in deciding whether he or she 
should remain on IP and ultimately continue participation in the study.  Patients do not 
necessarily have to have IP interrupted if they have self-injurious behavior that would be 
classified as nonsuicidal self-injurious behavior.
8.1.2. Permanent Discontinuation from Study Treatment
Investigational product should be permanently discontinued if the patient requests to discontinue 
IP.
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:

alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >8 x
upper limit of normal (ULN)

ALT or AST >5 x ULN for more than 2 weeks

ALT or AST >3 x ULN and total bilirubin level (TBL) >2 x ULN or 
international normalized ratio (INR) >1.5

ALT or AST >3 x ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, and/or rash 

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
alkaline phosphatase (ALP) >3 x ULN

ALP >2.5 x ULN and TBL >2 x ULN

ALP >2.5 x ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, and/or rash 
NOTE:  Patients who are discontinued from IP due to a hepatic event or liver test 
abnormality should have additional hepatic safety data collected via the hepatic safety 
eCRF.
Investigational product should be permanently discontinued if any of the following laboratory 
abnormalities are observed:

white blood cell count <1000 cells/L (1.00x103/L or 1.00 GI/L)

ANC <500 cells/L (0.50x103/L or 0.50 GI/L)

lymphocyte count <200 cells/L (0.20x103/L or 0.20 GI/L)

hemoglobin <6.5 g/dL (<65.0 g/L).
NOTE:  Temporary interruption rules (see Section 8.1.1) must be followed where 
applicable.  For laboratory values that meet permanent discontinuation thresholds, 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 JAHN.4) 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 (except for successfully treated basal or squamous cell skin 
carcinoma)

hepatitis B virus (HBV) DNA is detected with a value above limit of quantitation
or 2 sequential tests return a value of below the limit of quantitation (see 
Section 9.4.7).

certain prohibited medications are taken per Section 7.7.3 (Prohibited 
Medications and Procedures).

develop a VTE 
NOTE:  Patients who develop a VTE may have additional follow-up and testing recommended 
(see Appendix 7).  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.

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8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study treatment unless there 
are extenuating circumstances that make it medically necessary for the patient to continue on 
study treatment.  If the investigator and the sponsor clinical research physician (CRP) agree that
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.
8.2.
Discontinuation from the Study
Patients may choose to withdraw from the study for any reason at any time, and the reason for 
early withdrawal will be documented.
Some possible reasons that may lead to permanent discontinuation include the following:

enrollment in any other clinical trial 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 atopic dermatitis and becomes reimbursed or 
commercially available in that country or region, or a negative regulatory opinion 
is received in that country or region. 

investigator decision
o
the investigator decides that the patient should be discontinued from the study
o
if the patient, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new agent

patient decision
o
the patient requests to be withdrawn from the study
Patients discontinuing from the study prematurely for any reason should complete AE and other 
safety follow-up per Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety) of this protocol.
8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 

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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 3, Appendix 4, and Appendix 5 list the laboratory tests that will be performed for this 
study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Investigator’s Global Assessment
Validated Investigator’s Global Assessment for Atopic Dermatitis (vIGA-AD): The IGA 
used in this study, the vIGA-AD (referred to as the IGA throughout the protocol) measures the 
investigator’s global assessment of the patient’s overall severity of their AD, based on a static, 
numeric 5-point scale from 0 (clear skin) to 4 (severe disease).  The score is based on an overall 
assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
9.1.2. Eczema Area and Severity Index Scores
The EASI assesses extent of disease at 4 body regions and measures 4 clinical 
signs:(1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification each on a 
scale of 0 to 3. The EASI confers a maximum score of 72. The EASI evaluates 2 dimensions of 
AD: disease extent and clinical signs (Hanifin et al. 2001).
Body surface area affected by AD will be derived from data collected as part of the EASI 
assessment.
9.1.3. SCORing Atopic Dermatitis
The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical 
characteristics to determine disease severity: (1) erythema, (2) edema/papulation, 
(3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness. The SCORAD index also 
assesses subjective symptoms of pruritus and sleep loss.  These 3 aspects – extent of disease, 
disease severity, and subjective symptoms combine to give a maximum possible score of 
103 (Stalder et al. 1993; Kunz et al. 1997; Schram et al. 2012).
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 an electronic tablet and in countries where the questionnaires have been translated into the 
native language of the region and linguistically validated.

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9.1.4.1.
Patient-Oriented Eczema Measure
The POEM is a simple, 7-item, patient-administered scale that assesses disease severity in 
children and adults.  Patients respond to questions about the frequency of 7 symptoms (itching, 
sleep disturbance, bleeding, weeping/oozing, cracking, flaking, and dryness/roughness) over the 
past 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).
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.
Atopic Dermatitis Sleep Scale
The Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, patient-administered questionnaire 
developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of 
waking, and difficulty getting back to sleep last night. Patients rate their difficulty falling asleep 
and difficulty getting back to sleep, Items 1 and 3, respectively, using a 5-point Likert-type scale,
with response options ranging from 0 representing “not at all” to 4 representing “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.
9.1.4.4.
Skin Pain Numeric Rating Scale
Skin Pain NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 
0 representing “no pain” and 10 representing “worst pain imaginable.” Overall severity of a 
patient’s skin pain is indicated by selecting the number that best describes the worst level of skin 
pain in the past 24 hours.
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.
Dermatology Life Quality Index
The DLQI is a simple, patient-administered, 10-item, validated, quality-of-life questionnaire that 
covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, 
personal relationships, and treatment. The recall period of this scale is over the “last week.”  
Response categories include “not at all,” “a lot,” and “very much,” with corresponding scores of 
1, 2, and 3, respectively, and unanswered (“not relevant”) responses scored as 0. Scores range 
from 0 to 30, with higher scores indicating greater impairment of QoL. A DLQI total score of 
0 to 1 is considered as having no effect on a patient’s health-related QoL (Hongbo et al. 2005),
and a 4-point change from baseline is considered as the minimal clinically important difference 
threshold (Khilji et al. 2002; Basra et al. 2015).

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9.1.4.7.
European Quality of Life – 5 Dimensions – 5 Levels
The European Quality of Life–5 Dimensions–5 Levels (EQ-5D-5L) is a standardized measure of 
health status that provides a simple, generic measure of health for clinical and economic 
appraisal.  The EQ-5D-5L consists of 2 components:  a descriptive system of the respondent’s 
health and a rating of his or her current health state using a 0 to 100 mm visual analog scale 
(VAS).  The descriptive system comprises the following 5 dimensions:  mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression.  Each dimension has 5 levels:  no problems, 
slight problems, moderate problems, severe problems, and extreme problems.  The respondent is 
asked to indicate his or her health state by ticking (or placing a cross) in the box associated with 
the most appropriate statement in each of the 5 dimensions.  It should be noted that the numerals 
1 to 5 have no arithmetic properties and should not be used as an ordinal score.  The VAS 
records the respondent’s self-rated health on a vertical VAS where the endpoints are labeled 
“best imaginable health state” and “worst imaginable health state.”  This information can be used 
as a quantitative measure of health outcome.  The EQ-5D-5L health states, defined by the 
EQ-5D-5L descriptive system, may be converted into a single summary index by applying a 
formula that essentially attaches values (also called weights) to each of the levels in each 
dimension (Herdman et al. 2011; EuroQol Group 2015 [WWW]).
9.1.4.8.
Work Productivity and Activity Impairment Questionnaire – Atopic 
Dermatitis
The Work Productivity and Activity Impairment Questionnaire – Atopic Dermatitis (WPAI-AD) 
records impairment due to AD during the past 7 days. The WPAI-AD consists of 6 items 
grouped into 4 domains: absenteeism (work time missed), presenteeism (impairment at 
work/reduced on-the-job effectiveness), work productivity loss (overall work 
impairment/absenteeism plus presenteeism), and activity impairment. Scores are calculated as 
impairment percentages (Reilly et al. 1993), with higher scores indicating greater impairment 
and less productivity.
9.1.5. Appropriateness of Assessments
All assessments utilized in this study are standard, widely used, and generally recognized as 
reliable, accurate, and relevant, with the exception of ADSS and Skin Pain NRS, which are 
currently being developed and validated according to regulatory guidance.
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 

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be followed until the event resolves, stabilizes with appropriate diagnostic evaluation, or is 
reasonably explained.  The frequency of follow-up evaluations of the AE is left to the discretion 
of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the informed consent form (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 IP via eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment, or pathologies.  A “reasonable possibility” means that there is a 
cause-and-effect relationship between the 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.
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 (i.e., 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 

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should be reported to the sponsor as per SAE reporting requirements and timelines if it is 
considered reasonably possibly related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.  Patients with a serious hepatic AE should have additional data collected using the 
hepatic safety eCRF.
Pregnancy (during maternal or paternal exposure to 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 summary CRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he or she considers the event reasonably possibly related to 
the study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to IP or procedure.  United States 21 CFR 
312.32 and European Union Clinical Trial Directive 2001/20/EC and the associated detailed 
guidance or national regulatory requirements in participating countries require the reporting of 
SUSARs.  Lilly has procedures that will be followed for the recording and expedited reporting of 
SUSARs that are consistent with global regulations and the associated detailed guidance.
9.2.2. Adverse Events of Special Interest
Adverse events of special interest will include the following:

infections (including tuberculosis, herpes zoster, or opportunistic infections)

malignancies

hepatic events (see Section 9.4.8)

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 facilitate process and 
product improvements.

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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
Refer to the IB.
9.4.
Safety
Any clinically significant findings from electrocardiogram 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. Vital Signs
For each patient, vital sign measurements should be conducted according to the Schedule of 
Activities (Section 2).
9.4.2. Physical Exam
For each patient, physical examinations will be conducted according to the Schedule of 
Activities (Section 2).  Physical examinations throughout the study should include a 
symptom-directed physical examination.  A complete physical examination may be conducted at 
the investigator’s discretion at any time a patient presents with physical complaints.
9.4.3. Laboratory Tests
For each patient, laboratory tests detailed in Appendix 3, Appendix 4, Appendix 5, and Appendix 
7 should be conducted according to the Schedule of Activities (Section 2).  With the exception of 
laboratory test results that may unblind the study, Lilly or its designee will provide the 
investigator with the results of laboratory tests analyzed by a central vendor, if a central vendor 
is used for the clinical trial.
9.4.4. Hospital Anxiety Depression Scale
The Hospital Anxiety Depression Scale (HADS) is a 14-item self-assessment scale that 
determines the levels of anxiety and depression that a patient experienced over the past week. 
The HADS utilizes a 4-point Likert scale (e.g., 0 to 3) for each question and is intended for ages 
12 to 65 years (Zigmond and Snaith 1983; White et al. 1999). Scores for each domain (anxiety 
and depression) can range from 0 to 21, with higher scores indicating greater anxiety or 
depression (Zigmond and Snaith 1983; Snaith 2003).
9.4.5. Columbia-Suicide Severity Rating Scale
The C-SSRS captures the occurrence, severity, and frequency of suicidal ideation and/or 
behavior during the assessment period.  The scale includes suggested questions to solicit the type 
of information needed to determine if suicidal ideation and/or behavior occurred.  The C-SSRS is 
administered by an appropriately trained health care professional with at least 1 year of patient 
care/clinical experience.  The tool was developed by the National Institute of Mental Health trial 

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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 Supplement and Follow-Up Form
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. Hepatitis B Virus DNA Monitoring
Hepatitis B virus DNA testing will be performed in enrolled patients who tested positive for 
anti-hepatitis B core antibody (HBcAb) at screening for the originator study.
Patients who are HBcAb positive and HBV DNA negative (undetectable) at screening (Visit 1) 
for the originator study will require HBV DNA monitoring every 2 to 4 months and at the 
patients’ last visit, 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,” then patients will continue in JAHN and monitoring will
resume as per the 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.
9.4.8. Hepatic Safety Monitoring and Data Collection
If a study patient experiences elevated ALT ≥3 x ULN, ALP ≥2 x ULN, or elevated TBL ≥2 x
ULN, liver testing (Appendix 4) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator in consultation 

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with the study medical monitor.  Monitoring of ALT, AST, TBL, and ALP should continue until 
levels normalize or return to approximate baseline levels.
Discontinuation criteria of IPs, either temporary interruption or permanent discontinuation, due 
to abnormal ALT, AST, TBL, or ALP, are detailed in Section 8.1.
Additional safety data should be collected via the hepatic eCRF if 1 or more of the following 
conditions occur:

elevation of serum ALT to ≥5 x ULN on 2 or more consecutive blood tests

elevated serum TBL to ≥2 x ULN (except for cases of known Gilbert’s syndrome)

elevation of serum ALP to ≥2 x ULN on 2 or more consecutive blood tests

patient discontinued from treatment due to a hepatic event or abnormality of liver 
tests

hepatic event considered to be a SAE
See Section 8.1 for a description of hepatic laboratory values that are criteria for temporary 
interruption or permanent discontinuation of IP.
9.4.9. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.  Additionally, a DMC will oversee the conduct of this study and will periodically 
review safety data (Section 10.3.7.1).  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 
board (an advisory group for this study formed to protect the integrity of data; refer to Interim 
Analyses section [Section 10.3.7]) can conduct additional analyses of the safety data.
The Lilly CRP will monitor safety data throughout the course of the study.  Lilly will review 
SAEs within time frames mandated by company procedures.  The Lilly CRP will, as is 
appropriate, consult with the functionally independent Global Patient Safety 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 event and VTEs (Appendix 7).  Adverse event reports and vital signs will be 
collected at each study visit.  The cardiovascular monitoring plan includes the following:

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
regular monitoring of lipid levels

potential MACE (cardiovascular death, MI, stroke), other cardiovascular events (such as 
hospitalization for unstable angina, hospitalization for heart failure, serious arrhythmia, 
resuscitated sudden death, cardiogenic shock, coronary revascularization such as 
coronary artery bypass graft or percutaneous coronary intervention), venous thrombotic 
events, and noncardiovascular deaths will be identified by the investigative site or 
through medical review and will be sent to a blinded Clinical Event Committee for 
adjudication at regular intervals.
9.5.
Pharmacokinetics
Not applicable.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenetics
Not applicable.
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics, mechanism of action, variability of patient response (including 
safety), and clinical outcome.  Sample collection is incorporated into clinical studies to enable 
examination of these questions through measurement of biomolecules including DNA, 
ribonucleic acid, proteins, lipids, and other cellular elements.
Blood samples for non-pharmacogenetic 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 for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if local regulations and ethical review boards (ERBs) impose shorter time 
limits, at a facility selected by Lilly.  This retention period enables use of new technologies, 
response to regulatory questions, and investigation of variable response that may not be observed 
until later in the development of baricitinib or after baricitinib becomes commercially available.
9.9.
Medical Resource Utilization and Health Economics
Health Economics will be evaluated in this study utilizing the EQ-5D-5L and WPAI-AD 
(Section 9.1.4). Medical Resource Utilization parameters will not be evaluated in this study.

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10. Statistical Considerations
10.1. Sample Size Determination
It is anticipated that 95% of enrolled patients will complete Studies JAHL, JAHM, and JAIY and 
roll over into Study JAHN. Therefore, planned enrollment into Study JAHN from the 
originating Studies JAHL, JAHM, and JAIY will be approximately 1425 patients.  Of these 
patients, approximately 765 will start Study JAHN on baricitinib 4-mg, 547 on baricitinib 2-mg, 
34 on baricitinib 1-mg, and 79 on placebo. Patients who are considered nonresponders at entry 
into Study JAHN will be randomized 1:1 to either baricitinib 4-mg or baricitinib 2-mg and 
stratified by IGA 0, 1, 2, IGA 3 and IGA 4.  This study is meant to evaluate patients’ long-term 
response of baricitinib and the sample sizes are not determined to detect differences between 
baricitinib and placebo in a statistically powered manner.  Additional patients may enroll from 
addenda or other studies.
Patients at Week 52 will be stratified by responder status (IGA 0 or 1 versus IGA 2) when 
entering the randomized withdrawal and downtitration substudy. It is estimated that there will be 
approximately 600 patients entering into the randomized withdrawal and downtitration substudy.  
The substudy is meant to evaluate the change in clinical response after treatment withdrawal or 
downtitration and does not account for whether the sample size is sufficient to detect a difference 
between baricitinib and placebo. Maintenance of treatment benefit is defined as response of 
IGA 0, 1, or 2.
10.2. Populations for Analyses
Unless otherwise specified, the efficacy and health outcome analyses will be conducted on the
modified 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 and who received at 
least 1 dose of the IP in Study JAHN.  Unless otherwise specified, safety analyses will be 
conducted on the safety population, which is defined as all enrolled patients who received at least 
1 dose of the IP they were randomized to in Study JAHN.  Patients will be analyzed for efficacy, 
health outcomes, and safety according to the treatment to which they were assigned. Further 
details will be described in the SAP, including, but not limited to, additional populations for the 
randomized withdrawal and downtitration substudy.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee. A detailed 
SAP describing the statistical methodologies will be developed by Lilly or its designee.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.

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All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05, unless otherwise 
stated. Adjustment for multiple comparisons will not be carried out.
Primary and secondary discrete efficacy variables will be descriptively summarized by treatment 
group in terms of frequencies and percentages.  Treatment comparisons of discrete efficacy 
variables between treatment groups may be made using a logistic regression analysis with 
disease severity (IGA 0 or 1 versus IGA 2), and treatment group in the model.  Other factors may 
be included in the model. If the logistic regression model is performed, then the p-value from 
the logistic model, percentages, difference in percentages, and 100(1-alpha)% confidence 
interval (CI) of the difference in percentages using the Newcombe–Wilson method (Newcombe 
1998) without continuity correction will be reported.  The p-value from the Fisher exact test will 
also be produced.
Continuous efficacy variables will be descriptively summarized by treatment group in terms of 
number of patients, mean, standard deviation, median, minimum, and maximum. When 
evaluating these continuous measures over time, a restricted maximum likelihood-based mixed 
model for repeated measures (MMRM) may be used.  The model will include treatment, baseline 
severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline score 
and baseline score-by-visit-interaction as fixed continuous effects. Other factors may be 
included in the model. 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-square means (LSM) will be used for the statistical comparison; 
95% CI will also be reported. Further details on the use of MMRM will be described in the SAP.
Treatment comparisons of continuous efficacy and health outcome variables may also be made 
using analysis of covariance (ANCOVA) with disease severity, treatment group, and baseline 
value in the model. Other factors may be included in the model. If the ANCOVA is performed, 
then Type III tests for the LSM will be used for statistical comparison between treatment groups.  
The LSM difference, standard error, p-value, and 100(1-alpha)% CI may also be reported.  The 
method used to handle missing data will be specified in the SAP.
All safety data will be descriptively summarized by treatment groups. For categorical events, 
Fisher exact test may be used to perform comparisons between each baricitinib dose and the 
placebo group. Fisher exact test may also be used for the 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.
Time-to-an-event analysis may be done and would be analyzed using a Cox proportional hazards 
model with treatment and stratification variables in the model.  Hazard ratio with CIs may be 
reported.  Kaplan–Meier curves may also be produced. Diagnostic tests for checking the validity 
of proportional hazards assumption may be done and these would be described in more detail in 
the SAP. If the assumption of proportional hazards is not justified, nonproportionality may be 

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modeled by stratification, as the most likely variable that interacts with time is categorical, that 
is, disease severity.
Missing data imputation:
1. Nonresponder imputation (NRI):  All patients who either discontinue the study treatment 
or discontinue the study for any reason at any time will be defined as nonresponders for 
the NRI analysis for categorical variables such as IGA 0/1 or EASI 50/75/90 after rescue 
or discontinuation and onward.
2. MMRM:  Continuous variables such as EASI and SCORAD scores will be assumed to be 
missing after rescue or discontinuation and then a MMRM analysis will be performed.
3. Last observed carried forward:  An additional analysis may be done that uses the last 
observed value on or prior to discontinuation or rescue therapy.  This may 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 tipping point 
analyses as well as a reference-based multiple imputation method may be done and will be 
specified in the SAP.
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.  This will be done for Study JAHN as well as the randomized withdrawal
and downtitration substudy.  Additional summaries that may be produced for other populations 
will be documented in the SAP.  No formal statistical comparisons will be made among 
treatment groups.
10.3.2.2. Patient Characteristics
Demographic and baseline characteristics will be summarized descriptively by treatment group
for Study JAHN and for the randomized withdrawal and downtitration substudy.  Additional 
summaries that may be produced for other populations will be documented in the SAP.  
Descriptive statistics including number of patients, mean, standard deviation, median, minimum, 
and maximum will be provided for continuous measures, and frequency counts and percentages 
will be tabulated for categorical measures. No formal statistical comparisons will be made 
among treatment groups unless otherwise stated.
10.3.2.3. Concomitant Therapy
Concomitant medications will be descriptively summarized by treatment group in terms of 
frequencies and percentages.  The medications will be coded accordingly.
10.3.2.4. Treatment Compliance
Treatment compliance with the randomly assigned study medication will be evaluated at every 
clinic visit through the counts of returned study drug tablets. A patient will be considered 
significantly noncompliant if he or she misses more than 20% of the prescribed doses during the 

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study, that is, compliance <80%, unless the patient’s IP is withheld by the investigator. Similarly, 
a patient will be considered significantly noncompliant if he or she is judged by the investigator 
to have intentionally or repeatedly taken more than the prescribed amount of medication, that is,
compliance ≥120%.
10.3.3. Efficacy Analyses
Analyses will be conducted in Study JAHN from Week 0 to 52 as well as for the randomized 
withdrawal and downtitration substudy.  Discrete efficacy variables will be descriptively 
summarized by treatment group in terms of frequencies and percentages.  Treatment 
comparisons of categorical variables, such as IGA, will be analyzed using a logistic regression 
model described above. Other dichotomous secondary endpoints will be analyzed similarly. 
Nonresponder imputation will be used as described above. Additionally, time to retreatment
may be analyzed using Cox proportion hazard model along with Kaplan–Meier curves. If the 
assumption of proportional hazards is not justified, analysis will proceed using the proportion of 
patients who meet criteria for loss of treatment benefit.  Continuous efficacy variables will be 
descriptively summarized by treatment group in terms of number of patients, mean, standard 
deviation, median, minimum, and maximum. For continuous variables, data after 
discontinuation or rescue will be assumed to be missing and data may be analyzed using a 
MMRM model as described in Section 10.3.1.
10.3.4. Safety Analyses
All safety data will be descriptively summarized by treatment groups and analyzed using the 
safety population, unless otherwise stated.
Treatment-emergent adverse events (TEAEs) are defined as AEs that either first occurred or 
worsened in severity after the first dose of study treatment in Study JAHN. The number of 
TEAEs as well as the number and percentage of patients who experienced at least 1 TEAE will 
be summarized using Medical Dictionary for Regulatory Activities for each system organ class 
(or a body system) and each preferred term by treatment group. Serious adverse events and AEs 
that lead to study drug discontinuation will also be summarized by treatment group and treatment 
period.  Fisher exact test may be used to perform comparisons between treatment groups.  
Further details will be given in the SAP.
All clinical laboratory results will be descriptively summarized by treatment group and treatment 
period. Individual results that are outside of normal reference ranges will be flagged in data 
listings. Quantitative clinical hematology, chemistry, and urinalysis variables obtained at 
baseline to postbaseline visits will be summarized as changes from baseline by treatment group
and treatment period and may be analyzed using ANCOVA with treatment and baseline value in 
the model. Categorical variables, including the incidence of abnormal values and incidence of 
adverse events of special interest, will be summarized by frequency and percentage of patients in 
corresponding categories. Shift tables will be presented for selected measures.
Observed values and changes from baseline (predose or screening if missing) for vital signs and 
physical characteristics will be descriptively summarized by treatment group and treatment 

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period.  Change from baseline to postbaseline in vital signs, and body weight may be analyzed 
using ANCOVA with treatment and baseline value in the model.
The incidence and average duration of study drug interruptions may be summarized and 
compared descriptively among treatment group and treatment period. Various techniques may 
be used to estimate the effects of study drug interruptions on safety measures. Further analyses 
may be performed and will be planned in the SAP.
Data collected after initiation of rescue therapy will be summarized as appropriate.
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
Not applicable.
10.3.6. Other Analyses
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.  More detailed analytical 
methods will be described in the SAP.
10.3.6.1. Subgroup Analyses
To assess whether the treatment effect is similar across subgroups, a logistic model will be used 
and will include treatment, stratification variables, the subgroup variable (e.g., sex), and the 
subgroup by treatment interaction.  If the interaction is statistically significant at alpha=0.10, the 
nature of the interaction will be explored, that is, within each subgroup the treatment effect will 
be estimated.  Similarly, for continuous variable, the MMRM model will include additional 
variables for subgroup and the subgroup by treatment interaction.
Subgroups to be evaluated may include region, baseline severity, sex, age, race, prior therapy, etc.  
Further definitions for the levels of the subgroup variables, the analysis methodology, and any 
additional subgroup analyses will be defined in the SAP. All subgroup analyses will be treated 
as exploratory.
10.3.7. Interim Analyses
10.3.7.1. Data Monitoring Committee
A DMC will oversee the conduct of this trial.  The DMC will consist of members external to 
Lilly.  This DMC will follow the rules defined in the DMC charter, focusing on potential and 
identified risks for this molecule and for this class of compounds.  The membership of the DMC 
will include, at a minimum, specialists with expertise in dermatology, statistics, and other 
appropriate specialties.
The DMC will be authorized to review unblinded results of analyses by treatment group prior to 
database lock, including study discontinuation data, AEs including SAEs, clinical laboratory 
data, vital sign data, etc.  The DMC may recommend continuation of the study, as designed; 
temporary suspension of enrollment; or the discontinuation of a particular dose regimen or the 
entire study.  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.  However, the 

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study will not be stopped for positive efficacy results, and there is no planned futility assessment.  
Hence, no alpha is spent. As an extension of the DMC for the originating studies, interim 
analyses will be conducted for the DMC review on an approximate semiannual basis (this timing 
may be modified based on recruitment rates in originating studies).  Furthermore, details of the 
DMC will be documented in a DMC charter and interim analysis plan contained in the SAP.
Besides DMC members, 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, in 
order to initiate work for regulatory submission.  Interim locks may be conducted at various 
timepoints to support regulatory activities and scientific disclosures.  The timing of the data 
lock(s) for the analysis of the efficacy data from the sub-study will be determined by the 
retreatment rates.  Information that may unblind the study during the analyses will not be 
reported to study sites or blinded study team until the study has been unblinded.
Unblinding details are specified in a separate unblinding plan document.
10.3.7.2. Adjudication Committee
A blinded Clinical Event Committee will adjudicate potential MACE (cardiovascular death, MI, 
stroke), other cardiovascular events (such as hospitalization for unstable angina, hospitalization 
for heart failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary 
revascularization such as coronary artery bypass graft or percutaneous coronary intervention), 
venous thrombotic events, and noncardiovascular deaths.  Details of membership, operations, 
recommendations from the Committee, and the communication plan will be documented in the 
Charter.

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Ziegler SF, Roan F, Bell BD, Stoklasek TA, Kitajima M, Han H. The biology of thymic stromal 
lymphopoietin (TSLP). Adv Pharmacol. 2013;66:129-155.
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand.
1983;67:361-370.

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12. Appendices

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Appendix 1. Abbreviations and Definitions
Term
Definition
AD
atopic dermatitis
ADSS
Atopic Dermatitis Sleep Scale
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
A double-blind study is one in which neither the patient nor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received.
CI
confidence interval
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
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
CSR
clinical study report
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
EASI
Eczema Area and Severity Index
eCOA
electronic clinical outcome assessment

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eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the trial are 
those who have been assigned to a treatment.
Enter
Patients entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
EQ-5D-5L
European Quality of Life–5 Dimensions–5 Levels
ERB
ethical review board
ETV
early termination visit
FDA
the Food and Drug Administration
GCP
good clinical practice
HADS
Hospital Anxiety Depression Scale
HBcAb
anti-hepatitis B core antibody
HBV
hepatitis B virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IGA
Investigator’s Global Assessment
IL
interleukin
INR
international normalized ratio
investigational 
product (IP)
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IWRS
interactive web-response system
JAK
Janus kinase
LSM
least squares mean
MACE
major adverse cardiovascular events
MI
myocardial infarction

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MMRM
mixed model for repeated measures
NRI
nonresponder imputation
NRS
numeric rating scale
PK
pharmacokinetic
POEM
Patient-Oriented Eczema Measure
PRO/ePRO
patient-reported outcome/electronic patient-reported outcome
QD
once daily
QoL
quality of life
RA
rheumatoid arthritis
SAE
serious adverse event
SAP
statistical analysis plan
SCORAD
SCORing Atopic Dermatitis
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study.
SUSAR
suspected unexpected serious adverse reaction
TBL
total bilirubin level
TCNI
topical calcineurin inhibitor
TCS
topical corticosteroid(s)
TEAE
treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, which does not necessarily have to have a causal relationship 
with this treatment.
TSLP
thymic stromal lymphopoietin
TYK2
tyrosine kinase 2
ULN
upper limit of normal
VAS
visual analog scale
vIGA-AD
Validated Investigator’s Global Assessment for Atopic Dermatitis (referred to as the 
IGA throughout the protocol)
VTE
venous thromboembolic event (deep vein thrombosis or pulmonary embolism)
WPAI-AD
Work Productivity and Activity Impairment Questionnaire – Atopic Dermatitis

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Appendix 2. Study Governance Considerations
Appendix 2.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 2.1.1.
Informed Consent
The investigator is responsible for ensuring:

that the patient understands the nature of the study, the potential risks and 
benefits of participating in the study, and that their participation is voluntary.

that informed consent is given by each patient.  This includes obtaining the 
appropriate signatures and dates on the informed consent form (ICF) prior to 
the performance of any protocol procedures and prior to the administration of 
investigational product (IP).

answering any questions the patient may have throughout the study and 
sharing in a timely manner any new information that may be relevant to the 
patient’s willingness to continue his or her participation in the trial.

that a copy of the ICF is provided to the participant or the participant’s legal 
representative and is kept on file.

that the medical record includes a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the 
written consent was obtained.  The authorized person obtaining the informed 
consent must also sign the ICF.
Appendix 2.1.2.
Ethical Review
The investigator must give assurance that the ethical review board (ERB) was properly 
constituted and convened as required by International Council for Harmonisation (ICH) 
guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF 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:

the current Investigator’s Brochure (IB) and updates during the course of the 
study

ICF and Assent Form

relevant curricula vitae

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Appendix 2.1.3.
Regulatory Considerations
This study will be conducted in accordance with:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of
Medical Sciences International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third party.
Appendix 2.1.4.
Investigator Information
Physicians with a specialty in dermatology will participate as investigators in this clinical trial.
Appendix 2.1.5.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 2.1.6.
Final Report Signature
Lilly will select a qualified investigator(s) from among investigators participating in the design, 
conduct, and/or analysis of the study to serve as the clinical study report (CSR) coordinating 
investigator.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the CSR coordinating investigator.
The CSR coordinating investigator will sign the final CSR for this study, indicating agreement 
that, to the best of his or her knowledge, the report accurately describes the conduct and results 
of the study.
The sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 2.2. Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate

sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the case report 
forms (CRFs), and study procedures.

make periodic visits to the study site

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
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 2.2.1.
Data Capture System
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site into the sponsor-provided electronic data capture system.
Electronic patient-reported outcome (ePRO) measures (e.g., a rating scale) and electronic clinical 
outcome assessments (eCOAs) are entered into an ePRO/eCOA instrument at the time that the 
information is obtained.  In these instances, where there is no prior written or electronic source 
data at the site, the ePRO/eCOA instrument record will serve as the source.
If ePRO/eCOA records are stored at a third party site, investigator sites will have continuous 
access to the source documents during the study and will receive an archival copy at the end of 
the study for retention.
Any data for which the ePRO/eCOA instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file.
Case report form data will be encoded and stored in InForm.  Data managed by a central vendor, 
such as laboratory test data, will be stored electronically in the central vendor’s database system.  
Data will subsequently be transferred from the central vendor to the Lilly data warehouse.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

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Appendix 2.3. Study and Site Closure
Appendix 2.3.1.
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 2.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP. Study termination may 
occur in a specific country or region when baricitinib is approved for the treatment of AD and 
becomes reimbursed or commercially available in that country or region, or a negative regulatory 
opinion is received in that country or region.

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Appendix 3. Clinical Laboratory Tests
Hematologya,b
Clinical Chemistrya,b
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Absolute reticulocyte count
Potassium
Total bilirubin
Mean cell volume
Mean cell hemoglobin
Direct bilirubin
Alkaline phosphatase
Mean cell hemoglobin concentration
Alanine aminotransferase (ALT)
Leukocytes (WBC)
Aspartate aminotransferase (AST)
Platelets
Blood urea nitrogen (BUN)
Creatinine
Absolute counts of:
Cystatin C
Neutrophils, segmented
Uric acid
Neutrophils, juvenile (bands)
Calcium
Lymphocytes
Glucose
Monocytes
Albumin
Eosinophils
Total protein
Basophils
Estimated glomerular filtration rate (eGFR)c
Creatine phosphokinase (CPK)
Urinalysisa,b,d
Color
Lipidsa,e
Specific gravity
pH
Total cholesterol
Low-density lipoprotein
Protein
High-density lipoprotein
Glucose
Triglycerides
Ketones
Bilirubin
Other Testsa
Urobilinogen
Blood
Exploratory storage samples (serum, plasma, and 
mRNA)
Leukocyte esterase
Pregnancy Testf
Nitrite
HBV DNAg
Serum immunoglobulin (IgE)
Abbreviations: HBcAb = anti-hepatitis B core antibody; HBV = hepatitis B virus; mRNA = messenger ribonucleic 
acid; RBC = red blood cell; WBC = white blood cell.
a
Assayed by sponsor-designated laboratory.
b
Unscheduled or repeat blood chemistry, hematology, and urinalysis panels may be performed at the discretion of 
the investigator, as needed.
c
eGFR from serum creatinine calculated by the central laboratory using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) Creatinine 2009 equation.
d
Microscopic examination of sediment performed only if abnormalities are noted on the routine urinalysis.
e
Fasting lipid profile. Patients should not eat or drink anything except water for 12 hours prior to test. If a patient 
attends these visits in a nonfasting state, this will not be considered a protocol violation.
f
For all women of childbearing potential, local urine pregnancy tests will be performed at all visits.
g
HBV DNA testing will be done in those patients who are HBcAb+ at screening.

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

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Appendix 5. Liver Function Testing and Hepatic Safety 
Monitoring
Liver Function Testing and Hepatic Safety Monitoring
Analyte
Exclusion
Criteria
Additional 
Hepatic 
Testing
Hepatic eCRF 
Reporting
Temporary 
Interruption of 
IP
Permanent Discontinuation 
of IP after Consultation with 
the Lilly-Designated Medical 
Monitor
Protocol 
section
Section 6.2
Section 9.4.8
Section 9.4.8
Section 8.1.1
Section 8.1.2
ALT/
AST
≥2 x ULN
ALT ≥3 x 
ULN
ALT ≥5 x ULN 
on ≥2 
consecutive tests
≥5 x ULN

>8 x ULN

>5 x ULN for >2 weeks

>3 x ULN AND TBL 
>2 x ULN or INR >1.5

>3 x ULN with 
symptomsa
ALP
≥2x ULN
≥2x ULN
≥2x ULN on ≥2 
consecutive tests
No applicable 
criteria

>3 x ULN

>2.5 x ULN AND TBL 
>2 x ULN 

>2.5 x ULN with 
symptomsa
TBL
≥1.5 x ULN
≥2 x ULN
≥2 x ULN 
(excluding 
Gilbert’s 
syndrome)
No applicable 
criteria

ALT or AST >3 x ULN 
AND TBL >2 x ULN

ALP >2.5 x ULN AND 
TBL >2 x ULN
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
INR = international normalized ratio; IP = investigational product; TBL = total bilirubin level; ULN = upper 
level of normal.
a
Fatigue, nausea, vomiting, right upper-quadrant pain or tenderness, fever, and/or rash.

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Appendix 6. Classification of Potency for Topical 
Corticosteroids
Potency
Class
Topical Corticosteroid
Formulation
Ultra high
I
Clobetasol propionate
Cream 0.05%
Diflorasone diacetate
Ointment 0.05%
High
II
Amcinonide
Ointment 0.1%
Betamethasone dipropionate
Ointment 0.05%
Desoximetasone
Cream or ointment 0.025%
Fluocinonide
Cream, ointment, or gel 0.05%
Halcinonide
Cream 0.1%
III
Betamethasone dipropionate
Cream 0.05%
Betamethasone valerate
Ointment 0.1%
Diflorasone diacetate
Cream 0.05%
Triamcinolone acetonide
Ointment 0.1%
Moderate
IV
Desoximetasone
Cream 0.05%
Fluocinolone acetonide
Ointment 0.025%
Fludroxycortide
Ointment 0.05%
Hydrocortisone valerate
Ointment 0.2%
Triamcinolone acetonide
Cream 0.1%
V
Betamethasone dipropionate
Lotion 0.02%
Betamethasone valerate
Cream 0.1%
Fluocinolone acetonide
Cream 0.025%
Fludroxycortide
Cream 0.05%
Hydrocortisone butyrate
Cream 0.1%
Hydrocortisone valerate
Cream 0.2%
Triamcinolone acetonide
Lotion 0.1%
Low
VI
Betamethasone valerate
Lotion 0.05%
Desonide
Cream 0.05%
Fluocinolone acetonide
Solution 0.01%
VII
Dexamethasone sodium phosphate
Cream 0.1%
Hydrocortisone 
Lotion, cream, or ointment 2.5%
Hydrocortisone acetate
Cream 1%
Methylprednisolone acetate
Cream 0.25%
Source: WHO (1997) and Tadicherla et al. (2009).

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Appendix 7. Monitoring Tests for Confirmed VTE
Selected tests may be obtained in patients with a venous thromboembolic event (VTE) in 
consultation with Eli Lilly and Company, its designee, or the clinical research physician.  The 
choice and optimal timing of these tests will be directed by the patient’s management and may 
require ongoing follow-up after study discontinuation.
Protein C Functional
Protein S Clottable
Antithrombin III
APC Resistance
PT
APTT
Fibrinogen
Cardiolipin Antibodies
PT Gene
Factor VIII C Assay
Hexagonal Phase Phospholipid Neutralization
C-Reactive Protein
PTT Incubated Mixing 
Dilute Russell Viper Venom 
Platelet Neutralization 
Factor V Leiden 
MTHFR 
Thrombin Time 
Reptilase 
Fibrinogen Antigen 
Protein C Immunologic 
Protein S Immunologic 
Heparin fXa Inhibition 
Abbreviations:  APC = activated protein C; APTT = activated partial thromboplastin time; fXa = factor Xa; 
MTHFR = methylene tetrahydrofolate reductase; PT = prothrombin time; PTT = partial thromboplastin time.

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Appendix 8. Protocol Amendment I4V-MC-JAHN(c) 
Summary - A Phase 3 Multicenter, Double-Blind Study to 
Evaluate the Long-Term Safety and Efficacy of 
Baricitinib in Adult Patients with Atopic Dermatitis
Overview
Protocol I4V-MC-JAHN, A Phase 3 Multicenter, Double-Blind Study to Evaluate the Long-
Term Safety and Efficacy of Baricitinib in Adult Patients with Atopic Dermatitis, has been 
amended.  This amendment is substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20EC of the European Parliament and the council of the European Union.  The 
new protocol is indicated by amendment (c) 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.  Other minor typographical corrections and minor formatting changes not 
affecting content have been made in the document, and these changes are not identified in the 
amendment summary table or with strikethrough/underscore.
Amendment Summary for Protocol I4V-MC-JAHN Amendment (c)
Section # and Name
Description of Change
Brief Rationale
Title, Synopsis, Section 2, 
Table 1 - Schedule of 
Activities, and Section 4
Included an additional six visits to reflect 
the 2-year extension to the study.
Added additional exploratory endpoint 
reflecting extension of treatment period 2 
up to 200 weeks.
This will allow for additional long-
term safety information to be collected
and provide patients the opportunity to 
continue study treatment until the 
anticipated approval of baricitinib in 
this indication.
This endpoint was added to reflect that 
additional efficacy analyses may be 
performed beyond Week 104 up to 
200 weeks.  The exact timing of 
analyses will be determined by the 
retreatment rates within the sub-study.
Section 5.1 and Figure 
JAHN 1
Reflected the change of the extension of 
treatment period 2 by approximately two 
years.
Figure was updated to include the additional 
visits.
Updated language to incorporate 
additional patient visits.
Additional visits were incorporated 
into Figure JAHN 1.
Section 5.1.3, 5.1.4, and 
5.4
Updated visits that were added.
Reflected the extension of patient 
visits in treatment period 2.
Section 7.2
Updated week visit of when IP will be last 
distributed.
Reflected change in visit schedule 
(from Week 104 to 184).
Section 7.6
Treatment compliance updated.
The calculation of treatment 

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Section # and Name
Description of Change
Brief Rationale
compliance was updated to include 
visits 17-22/ET.
Section 7.7.1
Updated language to reflect that TCS will 
not be provided or reimbursed by the 
sponsor for the additional visits (TCS
supplied by the sponsor only during the first 
2 years).
The purpose for this extension is to 
allow patients the opportunity to 
continue to receive baricitinib while 
allowing clinicians and patients 
freedom to use TCS product/dosing 
form (e.g., cream, ointment) that is 
preferred and is available as part of 
local standard of care.
Section 7.7.3
Removed leukotriene inhibitors from 
prohibited medications.
Removed allergen immunotherapy from 
prohibited medications.
Updated to align with JAIY protocol.  
Evidence suggests leukotriene 
inhibitors have little impact to AD.
Due to the extended duration of the 
study, the sponsor anticipates some 
patients may require allergen 
immunotherapy for allergic 
conditions.
Section 8.1.1, 8.1.2, and 
9.4.9
Patients will be permanently discontinued 
after one VTE instead of two.
Discontinuation criteria for VTEs 
were updated to align with current 
safety protocols within the Atopic 
dermatitis and Systemic Lupus 
Erythematosus (SLE) programs for 
baricitinib.
Section 9.4.9
Updated cardiovascular monitoring plan.
This language was updated to reflect 
accurate details of the cardiovascular 
monitoring plan, as designated by the 
originating studies.
Section 8.2, and Appendix 
2.3.2
Added study discontinuation criterion.
In line with the 2-year extension, 
providing patients the opportunity to 
continue study treatment until the 
anticipated approval of baricitinib, in 
this indication. The discontinuation 
criterion was updated to reflect the 
possibility of study termination 
following the potential approval of 
baricitinib for the treatment of Atopic 
Dermatitis or its dismissal due to 
negative opinion within a given 
country.
Section 10.1
Updated sample size estimates for 
individual doses.
Sample size estimates for individual 
doses were corrected from the 
previous protocol version.  There was 
no change in the overall sample size 
estimate
Section 10.3.7.1
Updated wording related to Interim locks.
This study will provide long-term 
safety data to support regulatory 
submissions.  The wording related to 
study interim data locks was updated 
to make it clearer that multiple interim 
locks may occur to support these 
regulatory activities.  In addition, the 
timing of the data lock(s) for the 

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Section # and Name
Description of Change
Brief Rationale
analysis of the efficacy data from the 
sub-study will also be determined by 
the retreatment rates within the sub-
study.

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
A 24-year Phase 3 multicenter, double-blind long-term extension study to evaluate the 
safety and efficacy of placebo, baricitinib 1-mg, baricitinib 2-mg, and baricitinib 4-mg in 
adult patients with atopic dermatitis, including a blinded randomized treatment withdrawal
and randomized downtitration.
1. Synopsis
Summary of Study Design:
Study I4V-MC-JAHN (JAHN) is a Phase 3, multicenter, double-blind study to evaluate the long-term safety and 
efficacy of baricitinib (1-mg once daily, 2-mg once daily, and 4-mg once daily) in adult patients with AD for
approximately 2 up to 4 years.  The study population will include patients aged 18 years or older who completed an 
originating study (such as I4V-MC-JAHL, I4V-MC-JAHM, or 14V-MC-JAIY) and were eligible for enrollment into 
JAHN.  There is a single substudy included that will evaluate treatment withdrawal and dose downtitration.
Treatment Arms and Duration:
The treatment study duration will be up to 2 4 years.  The study consists of 3 study periods and 1 substudy:  
randomized treatment withdrawal and downtitration.
Treatment Period:  The full treatment period will last from Week 0/Visit 1 through Week 104200/Visit 1622.  
Patients will continue using emollients daily and topical corticosteroid (TCS) use will be permitted at the 
investigator’s discretion and provided automatically at the time of rescue or retreatment.
Treatment Period 2:  Week 52 (Visit 8) through Week 104 200 (Visit 1622):
Post-Treatment Follow-Up Period: This period spans from the last treatment visit at Week 104200/Visit 2216, or 
early termination visit to approximately 28 days following the last dose of IP.

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2.
Schedule of Activities
Table JAHN.1. I4V-MC-JAHN Schedule of Activities
Treatment Period 1
Treatment Period 2
Screening 
and 
Baseline 
Period
PTFU 
Period
Visit number
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
/ET
17
18
19
20
21
22/
ETs
801b
Weeks from entry 
into JAHN
0
4
8
16
24
36
48
52
56
60
64
68
76
84
92
104
120
136
152
168
184
200
108204
Visit tolerance 
interval (days) from 
entry into JAHN
0 to 56 from 
last visit of 
originating 
studyc
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±7
±7
±7
±7
±7
±7
28 ± 4 
after 
last 
dose
Procedures
Inclusion and 
exclusion criteria 
review
Xd
Informed consent
Xe
Abbreviated 
demographics
X
Clinical Assessments
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (BP and 
pulse)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-directed 
physical examinationf
X
X
X
X
X
X
X
X
X
X
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
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
X
X
X
X
ePRO (patient diary) 
dispensed
X
X
X
X
Xg
Xg
Xg
Xg
ePRO (patient diary) 
returned
X
X
X
X
X
Xg
Xg
Xg
Xg
Xh
Xh
Rerandomizationi, j
X
X
IWRS
Xj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP dispensedj
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP returned and 
compliance assessed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense TCS 
(as needed)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAHN(c) Clinical Protocol
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Treatment Period 1
Treatment Period 2
Screening 
and 
Baseline 
Period
PTFU 
Period
Visit number
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
/ET
17
18
19
20
21
22/
ETs
801b
Weeks from entry 
into JAHN
0
4
8
16
24
36
48
52
56
60
64
68
76
84
92
104
120
136
152
168
184
200
108204
Visit tolerance 
interval (days) from 
entry into JAHN
0 to 56 from 
last visit of 
originating 
studyc
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±7
±7
±7
±7
±7
±7
28 ± 4 
after 
last 
dose
Weigh (tube with cap) 
and record returned 
TCS (as needed)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
Physician-Assessed Efficacy Measures
IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SCORAD
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Health Outcomes Measures and Other Questionnairesk
POEM
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
WPAI-AD
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
EQ-5D-5L
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
Itch NRS
X
X
X
X
X
X
X
X
X
X
Xh
Xh
Skin Pain NRS
X
X
X
X
X
X
X
X
X
X
Xh
Xh
ADSS
X
X
X
X
X
X
X
X
X
X
Xh
Xh
PGI-S-AD
X
X
X
X
X
X
X
X
X
X
Xh
Xh
HADS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Xt
C-SSRSl and 
Self-Harm 
Supplement Form 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up 
Formm
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Clinical chemistryn
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Lipids (fasting)p
Xo
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
Xo
X
X
X
X
X
X
X
X
Xs
Xt
HBV DNAq
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancyr
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAHN(c) Clinical Protocol
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Treatment Period 1
Treatment Period 2
Screening 
and 
Baseline 
Period
PTFU 
Period
Visit number
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
/ET
17
18
19
20
21
22/
ETs
801b
Weeks from entry 
into JAHN
0
4
8
16
24
36
48
52
56
60
64
68
76
84
92
104
120
136
152
168
184
200
108204
Visit tolerance 
interval (days) from 
entry into JAHN
0 to 56 from 
last visit of 
originating 
studyc
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±4
±7
±7
±7
±7
±7
±7
28 ± 4 
after 
last 
dose
Serum 
immunoglobulin (IgE)
X
X
X
X
Xs
Stored serum and 
plasma samples for 
exploratory analysis
X
X
X
X
Xs
Stored blood for RNA 
analysis
X
X
X
X
Xs
b
Patients who have discontinued IP but remain in the study for more than 28 days without IP can combine their Visit 1622/ET with Visit 801 (follow-up visit).
s
An ET visit should be conducted if a patient discontinues from the study before Week 200.  Early termination visit activities do not need to be duplicated if 
occurring at the time of a scheduled visit.  Weighing of TCS, collection of WPAI-AD, EQ-5D-5L, HADS, urinalysis, serum IgE exploratory storage samples, 
RNA and biomarker samples should only be performed at the ET visit if it occurs at or before Week 104.
t
For V801, the weighing of TCS, and collection of WPAI-AD, EQ-5D-5L, HADS, and urinalysis should only be performed if it occurs at or before Week 104.  
NOTE:  Patients completing V16 and planning to sign ICF for amendment (c) can participate as long as they have not completed a V801.  

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4.Objectives and Endpoints
Table JAHN.2.
Objectives and Endpoints
5.1 Overall Design
Study I4V-MC-JAHN (JAHN) is a Phase 3, multicenter, double-blind study to evaluate the 
long-term safety and efficacy of daily baricitinib 1-mg, 2-mg, and 4-mg in patients with AD for 
approximately 2 4 years.  The study will consist of 3 study periods and 1 substudy:  randomized 
treatment withdrawal and downtitration.  Patients entering Study JAHN will be classified as 
“Responders and Partial Responders” or “Nonresponders.”  Figure JAHN.1 illustrates the study 
design.  The full visit schedule is outlined in the Study Schedule of Activities (Section 2).  
Patients who completed originating Studies I4V-MC-JAHL (JAHL) and I4V-MC-JAHM
(JAHM) may be eligible for enrollment into Study JAHN; there may also be additional studies 
developed that will be eligible to enroll patients directly into Study JAHN.
Exploratory objectives may include evaluating the response to baricitinib treatment regimens on clinical measures 
and patient-reported outcomes.  These endpoints may include dichotomous endpoints or change from baseline for 
the following measures:  IGA, EASI, SCORAD, POEM, DLQI, WPAI-AD, EQ-5D-5L, Itch NRS, ADSS Item 2 
score, Skin Pain NRS, PGI-S-AD.  Patients continuing on placebo as responders will be assessed during the 
long-term extension for relevant efficacy endpoints.  Assessments of efficacy may be performed beyond Week 104 
up to Week 200.  The timing of the data lock(s) for the analysis of the efficacy data from the sub-study will be 
determined by the retreatment rates (see Section 10.3.7).  

I4V-MC-JAHN(c) Clinical Protocol
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Figure JAHN.1.
Illustration of study design for clinical Protocol I4V-MC-JAHN.
5.1.3. Treatment Period 2:  52 to 104 200 Weeks
5.1.4. Post-treatment Follow-up Period
Patients who complete the study through Visit 16 22(Week 104 200) will have a post-treatment 
follow-up visit (Visit 801) approximately 28 days after the last dose of IP.
5.4 Scientific Rationale for Study Design
Atopic dermatitis is a chronic, relapsing inflammatory skin disorder (Bieber 2010).  Although
several therapies are available to patients for the treatment of flares, there are very limited 
options for long-term management.  Most patients rely on chronic use of emollients and 
intermittent use of TCS or topical calcineurin inhibitors (TCNIs) to regulate skin inflammation in 
response to flares.  In patients with moderate to severe disease, long-term disease control is not 
always achieved. In order to address this important medical need for a safe and effective 
long-term therapy, this study will allow for a longer treatment period (approximately 2 up to 4
years).

I4V-MC-JAHN(c) Clinical Protocol
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7.2 Method of Treatment Assignment
The IWRS will be used to assign blister packs, each containing double-blind IP tablets, to each 
patient, starting at Visit 1 (Week 0), and at each visit up to and including Visit 1521
(Week 92184).  Site personnel will confirm that they have located the correct blister packs by 
entering a confirmation number found on the blister packs into the IWRS.
7.6 Treatment Compliance
Patient compliance with IP will be assessed at Visit 2 through Visit 22 16 and at Early 
Termination during the treatment period by counting returned tablets.
7.7.1
Topical Corticosteroids and Other Topical Treatments
Choice of Topical Treatment

Triamcinolone cream 0.1% and/or hydrocortisone 2.5% ointment.  Where possible both 
of these treatments will be supplied by the sponsor during the first 2 years of the 
treatment period (dispensed at Visits 1-15), and use should be recorded via weight of 
returned tube as indicated in the SOA (Section 2).  In the event of these specific TCS 
being unavailable during the first 2 years, an alternate, equivalent-potency TCS may be 
provided by the sponsor.  Following Visit 15, patients may independently continue to use 
their TCS of choice as directed by their investigator, as per clinical practice, but these 
will not be provided by the sponsor and weight will not be recorded.  
o
In the event that the sponsor is unable to supply TCS during the first 2 years, 
commercially available triamcinolone 0.1% cream and/or hydrocortisone 2.5% 
ointment may be supplied by the sites.  Where providing triamcinolone 0.1% 
cream and/or hydrocortisone 2.5% ointment is not possible, an equivalent-potency 
TCS cream and/or ointment that is in line with local practices can be supplied.  
Refer to Appendix 6 for guidance on potency equivalence. 
o
If the TCS supplied by the sponsor during the first 2 years is not considered 
suitable for an individual patient, an equivalent-potency TCS cream and/or 
ointment that is in line with local practices can be supplied by the sites.  Refer to
Appendix 6 for guidance on potency equivalence.
7.7.3
Prohibited Medications and Procedures
Prohibited Medications and Procedures Not Requiring 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.  

leukotriene inhibitors (e.g., montelukast [Singulair], zafirlukast [Accolate], and 
zileuton [Zyflo])

allergen immunotherapy

I4V-MC-JAHN(c) Clinical Protocol
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LY3009104

phototherapy including PUVA (psoralen and ultraviolet A), ultraviolet B, tanning 
booth, and excimer laser

bleach baths
8.1.1
Temporary Interruption from Study Treatment
Table JAHN.4.
Criteria for Temporary Interruption of Investigational Product
Hold IP if the Following Laboratory Test Results or 
Clinical Events Occur:
IP May Be Resumed When:
WBC count <2000 cells/L
(<2.00x103/L or <2.00 GI/L)
WBC count 2500 cells/L
(≥2.50x103/L or ≥2.50 GI/L)
ANC <1000 cells/L
(<1.00x103/L or <1.00 GI/L)
ANC ≥1200 cells/L
(≥1.20x103/L or ≥1.20 GI/L)
Lymphocyte count <500 cells/L
(<0.50x103/L or <0.50 GI/L)
Lymphocyte count 750 cells/L
(≥0.75x103/L or ≥0.75 GI/L)
Platelet count <75,000/L
(<75x103/L or <75 GI/L)
Platelet count 100,000/L
(≥100x103/L or ≥100 GI/L)
eGFR <40 mL/min/1.73 m2 (from serum creatinine) for 
patients with originating study screening eGFR
≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 (from serum creatinine) for 
patients with originating study screening eGFR ≥40 to 
<60 mL/min/1.73 m2
eGFR 40 mL/min/1.73 m2
ALT or AST >5 x ULN
ALT and AST return to <2 x ULN, and IP is not 
considered to be the cause of enzyme elevation
Hemoglobin <8 g/dL (<80.0 g/L)
Hemoglobin 10 g/dL (≥100.0 g/L)
Symptomatic herpes zoster
All skin lesions have crusted and are resolving
Infection that, in the opinion of the investigator, merits the 
IP being interrupted
Resolution of infection
Clinical features of VTE (such as deep vein thrombosis or
pulmonary embolism) are presenta
After evaluation and institution of appropriate 
treatment of VTEb
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; eGFR = estimated glomerular filtration rate; IP = investigational product; ULN = upper limit 
of normal; VTE = venous thromboembolic event; WBC = white blood cell.
a
Evaluate promptly and institute appropriate treatment. If upon evaluation VTE is ruled out and no other 
temporary or permanent discontinuation criteria are met, then IP may be resumed.
b
If after evaluation and institution of treatment the investigator deems that the patient is still at significant risk, or 
if this would constitute a second VTE for the patient, then IP should be discontinued permanently.
Although temporary interruption of IP is not a requirement at times of increased potential risk of 
VTE (venous thromboembolic event; e.g., surgery, significant air travel, or other situations 
involving prolonged immobilization), the following appropriate VTE prophylaxis guidelines are 
is recommended to help manage the elevated risk under these circumstances.
8.1.2
Permanent Discontinuation from Study Treatment

develop a second VTE 

I4V-MC-JAHN(c) Clinical Protocol
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NOTE:  Patients who develop a VTE may have additional follow-up and testing recommended 
(see Appendix 7).
8.2 Discontinuation from the Study

study termination may occur in a specific country or region when baricitinib is 
approved for the treatment of atopic dermatitis and becomes reimbursed or 
commercially available in that country or region, or a negative regulatory opinion is 
received in that country or region.  
9.4.9
Safety Monitoring
Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular events and VTEs (Appendix 7).  Adverse event reports and vital signs will be 
collected at each study visit.  The cardiovascular monitoring plan includes the following:

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 interventions), venous thrombotic 
events, and noncardiovascular deaths will be identified by the investigative site or 
through medical review and will be sent to a blinded Clinical Event Committee for 
adjudication at regular intervals.
10.1   
Sample Size Determination
It is anticipated that 90% 95% of enrolled patients will complete Studies JAHL, JAHM, and 
JAIY and roll over into Study JAHN.  Therefore, planned enrollment into Study JAHN from the 
originating Studies JAHL, JAHM, and JAIY will be approximately 1425 patients.  Of these 
patients, approximately 465765 will start Study JAHN on baricitinib 4-mg, 348547 on baricitinib 
2-mg, 5834 on baricitinib 1-mg, and 9779 on placebo.  Patients who are considered 
nonresponders at entry into Study JAHN will be randomized 1:1 to either baricitinib 4-mg or 
baricitinib 2-mg and stratified by IGA 0, 1, 2, IGA 3 and IGA 4.  This study is meant to evaluate 
patients’ long-term response of baricitinib and the sample sizes are not determined to detect 
differences between baricitinib and placebo in a statistically powered manner.  Additional 
patients may enroll from addenda or other studies.
10.3.7.1
Data Monitoring Committee
Besides DMC members, a limited number of pre-identified individuals may gain access to the 
limited unblinded data, as specified in the unblinding plan, prior to the interim or final database 
lock, in order to initiate work for regulatory submission.  Interim locks may be conducted at 
various timepoints to support regulatory activities and scientific disclosures.  The timing of the 
data lock(s) for the analysis of the efficacy data from the sub-study will be determined by the 
retreatment rates.  Information that may unblind the study during the analyses will not be 
reported to study sites or blinded study team until the study has been unblinded.
Appendix 2.3.2.
Discontinuation of the Study

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LY3009104
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP.  Study termination may 
occur in a specific country or region when baricitinib is approved for the treatment of AD and 
becomes reimbursed or commercially available in that country or region, or a negative regulatory 
opinion is received in that country or region.

Leo Document ID = aa36d560-7ca0-4d7d-b51c-b18cc3da1f51
Approver: 
Approval Date & Time: 27-Nov-2019 01:30:10 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 27-Nov-2019 02:33:07 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 27-Nov-2019 14:09:49 GMT
Signature meaning: Approved
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