A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Operationally Seamless, Adaptive Phase 2/3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients With Severe or Very Severe Alopecia Areata
Phase: PHASE2
Conditions: Alopecia Areata
Sponsor: Eli Lilly and Company

Protocol !4V-MC-JAHO (e) 
 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Operationally Seamless, 
Adaptive Phase 2/3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients 
with Severe or Very Severe Alopecia Areata. 
 
NCT03570749 
 
Approval Date: 02-Nov-2020 

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Protocol I4V-MC-JAHO(e)
A Multicenter, Randomized, Double-Blind, Placebo-
Controlled, Operationally Seamless, Adaptive Phase 2/3 
Study to Evaluate the Efficacy and Safety of Baricitinib in 
Adult Patients with Severe or Very Severe Alopecia Areata
BRAVE-AA1
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
baricitinib (LY3009104), unless such persons are bound by a confidentiality agreement with 
Eli Lilly and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Baricitinib (LY3009104)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly on 21-May-2018
Amendment (a) Electronically Signed and Approved by Lilly on 28-Jun-2018
Amendment (b) Electronically Signed and Approved by Lilly on 30-Oct-2018
Amendment (c) Electronically Signed and Approved by Lilly on 18-Oct-2019
Amendment (d) Electronically Signed and Approved by Lilly on 11-May-2020 
Amendment (e) Electronically Signed and Approved by Lilly on approval date provided 
below.
Approval Date: 02-Nov-2020 GMT

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Table of Contents
Section
Page
Protocol I4V-MC-JAHO(e) A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled, Operationally Seamless, Adaptive Phase 2/3 
Study to Evaluate the Efficacy and Safety of Baricitinib in Adult 
Patients with Severe or Very Severe Alopecia Areata..........................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................18
3.
Introduction ......................................................................................................................25
3.1.
Study Rationale............................................................................................................25
3.2.
Background..................................................................................................................26
3.3.
Benefit/Risk Assessment..............................................................................................27
4.
Objectives and Endpoints..................................................................................................30
5.
Study Design.....................................................................................................................33
5.1.
Overall Design .............................................................................................................33
5.1.1.
Stage 1 (Includes Phase 2 Portion and Phase 3 Portion before 
Decision Point) ....................................................................................................37
5.1.2.
Decision Point......................................................................................................37
5.1.3.
Stage 2 (Remaining Portion of Phase 3 Study after the 
Decision Point) ....................................................................................................38
5.1.4.
Period 1:  Screening (-35 to -3 days) ....................................................................38
5.1.5.
Period 2:  Double-Blind Treatment Period (Weeks 0 – 36)...................................38
5.1.6.
Period 3:  Long-Term Extension ..........................................................................39
5.1.7.
Period 4:  Bridging Extension...............................................................................41
5.1.8.
Period 5:  Posttreatment Follow-Up......................................................................41
5.2.
Number of Participants.................................................................................................42
5.3.
End of Study Definition ...............................................................................................42
5.4.
Scientific Rationale for Study Design...........................................................................42
5.4.1.
Rationale for Use of an Adaptive Operationally Seamless 
Design..................................................................................................................43
5.5.
Justification for Dose ...................................................................................................44
5.5.1.
Rationale for Dose Adjustment for Renal Impairment ..........................................45
6.
Study Population...............................................................................................................46
6.1.
Inclusion Criteria..........................................................................................................46
6.2.
Exclusion Criteria ........................................................................................................48
6.3.
Lifestyle Restrictions....................................................................................................55

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6.4.
Screen Failures.............................................................................................................55
7.
Treatments........................................................................................................................56
7.1.
Treatments Administered .............................................................................................56
7.1.1.
Packaging and Labelling ......................................................................................56
7.2.
Method of Treatment Assignment ................................................................................57
7.2.1.
Selection and Timing of Doses.............................................................................57
7.2.2.
Dose Adjustment for Renal Impairment ...............................................................58
7.3.
Blinding .......................................................................................................................58
7.4.
Dosage Modification....................................................................................................59
7.5.
Preparation/Handling/Storage/Accountability...............................................................59
7.6.
Treatment Compliance .................................................................................................59
7.7.
Concomitant Therapy...................................................................................................59
7.7.1.
Permitted Medications and Procedures.................................................................60
7.7.2.
Prohibited Medications and Procedures................................................................60
7.8.
Treatment after the End of the Study............................................................................61
7.8.1.
Continued Access.................................................................................................61
8.
Discontinuation Criteria ....................................................................................................62
8.1.
Discontinuation from Study Treatment.........................................................................62
8.1.1.
Permanent Discontinuation from Investigational Product .....................................62
8.1.2.
Temporary Interruption of Investigational Product ...............................................63
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................65
8.2.
Discontinuation from the Study....................................................................................65
8.3.
Lost to Follow-Up........................................................................................................66
9.
Study Assessments and Procedures ...................................................................................67
9.1.
Efficacy Assessments...................................................................................................67
9.1.1.
Primary Efficacy Assessments .............................................................................67
9.1.1.1.
Severity of Alopecia Tool (SALT) Score........................................................67
9.1.2.
Secondary Efficacy Assessments..........................................................................67
9.1.2.1.
Alopecia Areata Patient-Reported Outcomes ..................................................67
9.1.2.1.1.
Patient Reported Outcomes for Scalp Hair 
Assessment...............................................................................................67
9.1.2.1.2.
Other Patient Reported Outcomes for Appearance of 
Eyebrows, Appearance of Eyelashes, Eye Irritation, 
and Nail Appearance.................................................................................67
9.1.2.2.
Other Clinician-Reported Outcomes for Eyebrow Hair 
Loss Eyelash Hair Loss, and Nail Appearance ................................................68
9.1.3.
Health Outcomes and Quality-of-Life Measures...................................................68
9.1.3.1.
Skindex-16 Adapted for Alopecia Areata (Stage 2 Only) ................................68

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9.1.3.2.
Medical Outcomes Study 36-Item Short-Form Health 
Survey Version 2 Acute..................................................................................68
9.1.3.3.
EQ-5D-5L ......................................................................................................68
9.1.3.4.
Hospital Anxiety and Depression Scale ..........................................................69
9.1.4.
Photography.........................................................................................................69
9.1.5.
Alopecia Areata – Investigator Global Assessment...............................................70
9.1.6.
Appropriateness of Assessments ..........................................................................70
9.2.
Adverse Events ............................................................................................................70
9.2.1.
Serious Adverse Events........................................................................................71
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................72
9.2.2.
Adverse Events of Special Interest .......................................................................72
9.2.3.
Complaint Handling.............................................................................................72
9.3.
Treatment of Overdose.................................................................................................73
9.4.
Safety...........................................................................................................................73
9.4.1.
Electrocardiograms ..............................................................................................73
9.4.2.
Vital Signs ...........................................................................................................73
9.4.3.
Physical Examination...........................................................................................73
9.4.4.
Laboratory Tests ..................................................................................................73
9.4.5.
Columbia Suicide Severity Rating Scale...............................................................73
9.4.6.
Self-Harm and Follow-Up Supplement Forms......................................................74
9.4.7.
Chest X-Ray and Tuberculosis Testing.................................................................74
9.4.8.
Hepatitis B Virus DNA Monitoring......................................................................74
9.4.9.
Venous Thromboembolism Assessment ...............................................................75
9.4.10.
Safety Monitoring ................................................................................................75
9.4.10.1.
Hepatic Safety Monitoring..............................................................................76
9.5.
Pharmacokinetics .........................................................................................................76
9.6.
Pharmacodynamics ......................................................................................................78
9.7.
Pharmacogenomics ......................................................................................................78
9.7.1.
Whole Blood Samples for Pharmacogenetic Research..........................................78
9.8.
Biomarkers...................................................................................................................78
9.9.
Medical Resource Utilization and Health Economics ...................................................79
10.
Statistical Considerations ..................................................................................................80
10.1. Sample Size Determination ..........................................................................................80
10.2. Populations for Analyses..............................................................................................81
10.3. Statistical Analyses ......................................................................................................81
10.3.1.
General Statistical Considerations ........................................................................81
10.3.1.1.
Analysis Methods...........................................................................................82
10.3.1.2.
Missing Data Imputation ................................................................................83

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10.3.1.3.
Multiple Comparisons/Multiplicity.................................................................84
10.3.2.
Treatment Group Comparability...........................................................................87
10.3.2.1.
Patient Disposition..........................................................................................87
10.3.2.2.
Patient Characteristics ....................................................................................87
10.3.2.3.
Concomitant Therapy .....................................................................................87
10.3.2.4.
Treatment Compliance....................................................................................87
10.3.3.
Efficacy Analyses ................................................................................................88
10.3.3.1.
Primary Analyses ...........................................................................................88
10.3.3.2.
Secondary Analyses........................................................................................88
10.3.3.3.
Exploratory Analyses .....................................................................................88
10.3.4.
Safety Analyses....................................................................................................88
10.3.5.
Pharmacokinetic Analyses....................................................................................89
10.3.6.
Other Analyses.....................................................................................................89
10.3.6.1.
Subgroup Analyses.........................................................................................89
10.3.7.
Interim Analyses..................................................................................................90
10.3.7.1.
Decision Point Committee ..............................................................................90
10.3.7.2.
Data Monitoring Committee ...........................................................................90
10.3.7.3.
Other Interim Analyses...................................................................................91
10.3.7.3.1.
Phase 2 Week 36 Interim Analysis............................................................91
10.3.7.3.2.
Week 36 Primary Outcome Analysis and Other 
Regulatory Submission Activities .............................................................91
10.3.7.4.
Adjudication Committee.................................................................................91
11.
References ........................................................................................................................93
12.
Appendices .......................................................................................................................96

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List of Tables
Table
Page
Table JAHO.1.
Schedule of Activities....................................................................................19
Table JAHO.2.
Objectives......................................................................................................30
Table JAHO.3.
Treatment Regimen .......................................................................................56
Table JAHO.4.
Criteria for Temporary Interruption of Investigational Product.......................64

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List of Figures
Figure
Page
Figure JAHO.1. Illustration of randomization schemes and enrollment during the 
2 stages of the protocol, before and after the Decision Point. .........................34
Figure JAHO.2. Illustration of study design for Clinical Protocol I4V-MC-JAHO...................36
Figure JAHO.3. Graphical testing procedure for I4V-MC-JAHO.............................................85

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................97
Appendix 2.
Clinical Laboratory Tests.............................................................................102
Appendix 3.
Study Governance Considerations................................................................104
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality..................109
Appendix 5.
Liver Function Testing and Hepatic Safety Monitoring................................110
Appendix 6.
Additional Information on Statistical Methods.............................................111
Appendix 7.
Monitoring Tests for Confirmed VTE..........................................................115
Appendix 8.
Provisions for Changes in Study Conduct During Exceptional 
Circumstances .............................................................................................116
Appendix 9.
Protocol Amendment I4V-MC-JAHO(e) Summary......................................120

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1. Synopsis
Title of Study:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Operationally Seamless, 
Adaptive Phase 2/3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients 
with Severe or Very Severe Alopecia Areata.
Rationale:
Although, in the past, alopecia areata (AA) has been considered by some to be a benign 
condition, severe AA is now recognized as a significant medical condition with emotional and 
psychosocial distress, including high prevalence of depression and anxiety (Colon et al. 1991; 
Hunt and McHale 2005; Villasante Fricke and Miteva 2015).  Additionally, reduction in health-
related quality of life experienced by patients with AA has been well-documented (Jankovic et 
al. 2016; Liu et al. 2016; Rencz et al. 2016). Alopecia areata can be reversible – either 
spontaneously or after various types of treatments, but results are inconsistent (Islam et al. 2015)
and there is currently no Food and Drug Administration- (FDA-) approved treatment for AA. 
Baricitinib is an orally available, selective inhibitor of Janus kinases (JAKs).  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 tyrosine kinase 2 (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 and JAK2 and less potency for JAK3 or TYK2 (Fridman et al. 2010).  
Dual inhibition of JAK1 and JAK2, which may interrupt interferon gamma (IFNsignaling and 
other inflammatory pathways that contribute to the immunopathogenesis of AA, and clinical 
evidence with other JAK inhibitors support the investigation of baricitinib in the treatment of 
AA. This adaptive, operationally seamless, Phase 2/3, placebo-controlled study is designed to 
select up to 2 doses of baricitinib and assess their efficacy and safety for the treatment of severe 
(Severity of Alopecia Tool [SALT] score of 50% to 94%) and very severe AA (SALT score of 
95% to 100%).  Additionally, it will include a randomized withdrawal to explore the persistence 
of treatment effects and efficacy of retreatment upon relapse.  This operationally seamless design 
will provide longer-term safety data earlier in the clinical development program, compared to 
running separate Phase 2 and Phase 3 studies.
Results from the interim analysis of the Phase 2 portion of Study JAHO showed that the 2-mg 
and 4-mg baricitinib doses demonstrated numerical superiority over placebo and the 1-mg dose 
in hair regrowth after 12 (SALT30) and 16 (SALT50) weeks of treatment with no new safety 
signal. These results have been confirmed by a second interim analysis of Phase 2 portion of 
Study JAHO where the 2-mg dose and 4-mg dose were statistically significantly superior to 
placebo on the primary endpoint (SALT≤20) after 36 weeks of treatment. 

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Objective(s)/Endpoints:
Objectives
Endpoints
Primary Objective 
To test the hypothesis that the 4-mg dose or 2-mg dose
of baricitinib is superior to placebo in the treatment of 
patients with severe or very severe AA

Proportion of patients achieving SALT ≤20 at 
Week 36.
Key Secondary Objectives (Double–Blind, Placebo-Controlled Treatment Period)
These are pre-specified objectives that will be adjusted for multiplicity.
To compare the efficacy of baricitinib 4-mg or 2-mg 
to placebo in AA during the double-blind, placebo-
controlled treatment period as measured by physician-
assessed signs and symptoms of AA

Proportion of patients achieving SALT ≤20 at 
Weeks 16 and 24

Percent change from baseline in SALT score at 
Week 36.

Proportion of patients achieving a SALT50at Week 12.  

Proportion of patients achieving a SALT90 at Week 36.

Proportion of patients achieving an absolute SALT ≤10 
at Weeks 24 and 36.

Proportion of patients achieving ClinRO Measure for 
EB Hair Loss 0 or 1 with ≥2-point improvement from 
Baseline at Week 36 (among patients with ClinRO
Measure for EB Hair Loss ≥2 at Baseline)

Proportion of patients achieving ClinRO Measure for 
EL Hair Loss 0 or 1 with ≥2-point improvement from 
Baseline at Week 36 (among patients with ClinRO 
Measure for EL Hair Loss ≥2 at Baseline).
To compare the efficacy of baricitinib 4-mg or 2-mg
to placebo in AA during the double-blind, placebo-
controlled treatment period as assessed by a PRO
measure

Proportion of patients with PRO for Scalp Hair 
Assessment score of 0 or 1 with a ≥2-point 
improvement from Baseline at Week 36 among 
patients with a score of ≥3 at Baseline.
Other Secondary Objectives (Double–Blind, Placebo-Controlled Treatment Period)
These are pre-specified objectives that will NOT be adjusted for multiplicity.
To compare the efficacy of baricitinib 4-mg or 2-mg
to placebo in AA during the double-blind, placebo-
controlled treatment period as measured by physician-
assessed signs and symptoms of AA

Proportion of patients achieving SALT50 at Weeks 16, 
24, and 36.

Proportion of patients achieving a SALT75 at Weeks 24 
and 36.

Proportion of patients achieving a SALT90 at Week 24

Change from Baseline in SALT score at Weeks 12, 
16, 24, and 36.

Percent change from Baseline in SALT score at 
Weeks 12, 16, and 24.

Time to achieve SALT ≤20.

Proportion of patients achieving SALT100 at Weeks 24 
and 36.

Proportion of patients achieving ClinRO Measure for 
EB Hair Loss 0 or 1 with ≥2-point improvement from 
baseline at Weeks 16 and 24 (among patients with 
ClinRO Measure for EB Hair Loss ≥2 at Baseline).

Proportion of patients achieving ClinRO Measure for 
EL Hair Loss 0 or 1 with ≥2-point improvement from 

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Objectives
Endpoints
baseline at Weeks 16 and 24 (among patients with 
ClinRO Measure for EL Hair Loss ≥2 at Baseline).
To compare the efficacy of baricitinib 4-mg or 2-mg 
to placebo in AA during the double-blind, placebo-
controlled treatment period as assessed by PRO
measures and quality of life tools

Proportion of patients with PRO for Scalp Hair 
Assessment score of 0 or 1 with a ≥2-point 
improvement from Baseline at Weeks 12 and 24 
among patients with a score of ≥3 at Baseline

Proportion of patients achieving PRO Measure for EB 
0 or 1 with ≥2-point improvement from baseline at 
Weeks 16, 24, and 36 (among patients with PRO
Measure for EB ≥2 at Baseline)

Proportion of patients achieving PRO Measure for EL 
0 or 1 with ≥2-point improvement from baseline at 
Weeks 16, 24, and 36 (among patients with PRO
Measure for EL ≥2 at Baseline)

Mean change from Baseline in HADS-A and HADS-
D total scores at Weeks 24 and 36
Other Secondary (Patients entering Randomized Withdrawal)
These are pre-specified objectives that will NOT be adjusted for multiplicity.
To compare the maintenance of efficacy for patients 
randomized to remain on baricitinib, compared with 
patients randomized to placebo at Week 52 of the 
long-term extension period, as measured by 
physician-assessed signs of AA

Proportion of patients maintaining SALT ≤20 at 
Weeks 64, 76, 88, 104, 120, 136, 152, 168, 184, and 
200.

Proportion of patients experiencing a loss of treatment 
benefit (>20-point absolute worsening in SALT score) 
at Weeks 64, 76, 88, 104, 120, 136, 152, 168, 184, and 
200.

Time to loss of treatment benefit (>20-point absolute 
worsening in SALT score).
For patients experiencing loss of treatment benefit 
after randomization to placebo at Week 52:

To evaluate the recapture of efficacy for patients 
who were retreated after experiencing a loss of 
treatment benefit during the long-term 
maintenance period as measured by physician-
assessed signs of AA

Proportion of patients that achieve a SALT ≤20 at 12, 
16, 24, and 36 weeks of retreatment with baricitinib.

Percent change in SALT score at 12, 16, 24, and 
36 weeks of retreatment with baricitinib.

To evaluate the recapture of efficacy for patients 
who were retreated after experiencing a loss of 
treatment benefit during the long-term 
maintenance period as assessed by PRO and 
quality of life tools

Proportion of patients with a PRO for Scalp Hair 
Assessment score of 0 or 1 at 12, 16, 24, and 36 weeks 
of retreatment with baricitinib.
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:  SALT, AA-IGA, SALT30, ClinROs for Nail Appearance, Eyebrows, and/or Eyelash Hair Loss, 
PROs for Scalp Hair Assessment, Eyebrows, and Eyelashes, Nail Appearance and Eye Irritation, Skindex-16 AA, 
SF-36, EQ-5D-5L, HADS.  Assessments of efficacy may be performed beyond Week 104 up to Week 200. In 
addition, baricitinib pharmacokinetics will be characterized in the AA population and relationships between exposure 
and study endpoints will be explored.

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Abbreviations:  AA = alopecia areata; AA-IGA = Alopecia Areata Investigator Global Assessment; 
ClinRO = clinician-reported outcome; EB = eyebrow; EL = eyelash; EQ-5D-5L = European Quality of Life –
5 Dimensions – 5 Level; HADS = Hospital Anxiety and Depression Scale; PRO = patient-reported outcome; 
SALT = Severity of Alopecia Tool; SALT30 = at least 30% improvement from Baseline in SALT score; 
SALT50 = at least 50% improvement from Baseline in SALT score; SALT75 = at least 75% improvement from 
Baseline in SALT score; SALT90 = at least 90% improvement from Baseline in SALT score; SALT100 = 100% 
improvement from Baseline in SALT score; SF-36 = Short Form-36 Health Survey acute version 2; Skindex-16 
AA = Skindex-16 Adapted for Alopecia Areata.

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Summary of Study Design:
Study I4V-MC-JAHO (JAHO) is an adaptive, operationally seamless, Phase 2/3, multicenter, 
randomized, double-blind, placebo-controlled, parallel-group, outpatient study designed to 
identify up to 2 doses of baricitinib to be evaluated further in the Phase 3 portion of the study.  In 
Phase 3, efficacy and safety of 2-mg once daily (QD) and 4-mg QD doses of baricitinib will be 
compared to placebo in adult patients with severe (SALT score of 50% to 94%) or very severe 
(SALT score of 95% to 100%) scalp AA.  Approximately 725 adult patients will be enrolled into 
Study JAHO.  Approximately 100 patients will be enrolled into the Phase 2 portion of the study 
and approximately 625 patients will be enrolled into the Phase 3 portion of the study.
Patients must have a current AA episode of more than 6 months’ duration prior to screening 
(Visit 1), with at least 50% scalp involvement at screening AND Baseline (Visits 1 and 2) with 
no spontaneous improvement (no more than a 10 point reduction in SALT) over the past 6 
months. Patients with a current episode of severe or very severe AA of more than 8 years will 
not be eligible for inclusion in the study unless episodes of regrowth, spontaneous or under 
treatment, have been observed on the affected areas of the scalp over the past 8 years.  
Study Stages and Treatment Arms
The enrollment of patients in the study will be divided into 2 stages, which are separated by the 
Decision Point.  Different randomization schemes at Baseline (Visit 2) will be used by the 
interactive web-response system (IWRS) (during Stage 1 [Phase 2], Stage 1 [Phase 3] and 
Stage 2).

Stage 1: The time from study start until the Decision Point.  A maximum of 
approximately 300 patients will be randomized during Stage 1, before the Decision Point.
The first approximately 100 randomized patients will comprise the Phase 2 portion of the 
study and will be randomized in a 1:1:1:1 ratio to receive placebo QD, baricitinib 1-mg 
QD, baricitinib 2-mg QD, or baricitinib 4-mg QD.  An interim analysis will be conducted 
when the first approximately 100 patients who have been randomized and received 
treatment have reached Week 12 or have discontinued prior to Week 12. The remaining 
approximately 200 patients enrolled during Stage 1 will contribute patients to the Phase 3 
portion of the study and will be randomized at a 2:2:3 ratio to receive placebo QD, 
baricitinib 2-mg QD, or baricitinib 4-mg QD.

Decision Point:  The point in time when up to 2 baricitinib doses will be selected to 
continue in Stage 2 or the study will be stopped for futility, based on the outcome of the 
interim analysis. After the Decision Point, up to 3 treatments arms will continue into 
Stage 2: placebo; baricitinib low dose (lowest dose remaining in the study); and 
baricitinib high dose (highest dose remaining in the study). 

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
Stage 2: The time after the Decision Point until the end of the study during which the 
remaining patients (approximately 425 patients) will be enrolled into the Phase 3 portion 
of the study and randomized at a ratio of 2:2:3 to receive placebo QD, baricitinib low 
dose QD, or baricitinib high dose QD.  

Based on the Week 12 interim analysis of the Phase 2 population of this study, baricitinib 
2-mg QD (low dose) and baricitinib 4-mg QD (high dose) were selected at the Decision 
Point to continue into Stage 2 of Study JAHO.
Transitioning Patients After Decision Point 

After the Decision Point, patients who were enrolled in the baricitinib dose group that is 
discontinued (1-mg) will transition to the highest dose of baricitinib remaining in the 
study (4-mg).  

Patients and sites will remain blinded to treatment allocation after the Decision Point and, 
therefore, will not know which patients will be transitioned.  Transition will 
automatically occur at the next visit after Decision Point; this will be referred to as the 
Transition Visit.  A patient should be seen within 8 weeks following the Decision Point 
being communicated to the sites.  If there is not a regularly scheduled visit during this 
timeframe, patients may be brought in for an unscheduled visit. A patient should be seen 
within 8 weeks following the Transition Visit to obtain laboratory values for safety 
review.  If there is not a regularly scheduled visit during this timeframe, patients may be 
brought in for an unscheduled visit.  After the Decision Point, all patients enrolled during 
Stage 1 will follow all protocol procedures for Periods 2, 3 and 4.  
Number of Participants:
Planned enrollment is approximately 100 patients in the Phase 2 portion and approximately 
625 patients in the Phase 3 portion.  A maximum of approximately 300 patients will be enrolled 
during Stage 1 (approximately 100 patients in Phase 2 and approximately 200 patients in 
Phase 3).  The remaining approximately 425 patients for Phase 3 will be enrolled during Stage 2.
Study Design
The study design includes 5 periods:  a 5-week screening period; a 36-week double-blind, 
placebo-controlled treatment period; a 68-week long-term extension period; a 96-week bridging 
extension, and a posttreatment follow-up period.  The Schedule of Activities (SOA) will be the 
same for patients randomized during Stage 1 and Stage 2, except that some patients randomized 
during Stage 1 might have one or more unscheduled visits after the Decision Point:

Period 1:  Screening period (Visit 1) is between 3 and 35 days prior to Visit 2 (Week 0).

Period 2:  36-week double-blind, placebo-controlled treatment period is from Week 0 
(Baseline; Visit 2) to Week 36 (Visit 8).

Period 3:  68-week, long-term extension period with randomized withdrawal (for 
responders) is from Week 36 (Visit 8) to Week 104 (Visit 18).

Period 4:  Bridging Extension: from Week 104 (Visit 18) and up to Week 200 (Visit 24).  
Subjects who have completed Week 104 and have not met criteria of permanent 

I4V-MC-JAHO(e) Clinical Protocol
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discontinuation will have the possibility to remain in the trial for up to 96 additional 
weeks (up to Week 200). 

Period 5:  Posttreatment follow-up period; the posttreatment follow-up visit should occur 
approximately 4 weeks after the last dose of investigational product (IP) (i.e., 4-weeks 
after Week 200 (Visit 24) or the Early Termination Visit [ET]). 
Note:  Patients who have discontinued IP and remain in the study for more than 28 days 
without IP will have an ET; however, a separate follow-up visit (V801) is not required.
Patients who have completed Week 200 and will continue on marketed product beyond 
Week 200 do not need to complete Period 5 (Visit 801). 
At Week 36 
The predicted enrollment rate for Study JAHO suggests that some of the patients enrolled during 
Stage 1 may reach Week 36 before the Decision Point is achieved:  

Patients in the placebo treatment arm who have not achieved a SALT ≤20 at Week 36 
AND who reach the Week 36 Visit 
o
prior to the Decision Point, will be rescued to baricitinib and randomized in a 1:1 
ratio to baricitinib 2-mg or baricitinib 4-mg.
o
after the Decision Point, will be rescued to baricitinib and randomized in a 1:1 
ratio to baricitinib 2-mg or baricitinib 4-mg. 

Patients in the placebo arm who have achieved a SALT ≤20 will remain on placebo at 
Week 36.  These patients who have experienced spontaneous regrowth will remain on 
placebo for the remainder of the trial, even if relapse is observed later during the study.

All patients in the baricitinib treatment arms will continue in their current treatment 
group regardless of their treatment response at Week 36 (refer to Week 52 and Week 76 
sections below for additional rescue information and discontinuation criteria).
At Week 52
Responders (SALT ≤20)

Patients in baricitinib treatment arms who achieve a SALT ≤20 at Week 52 (responders) 
are eligible for randomized withdrawal, provided that they have stayed on the same dose 
of baricitinib from initial randomization (Visit 2).  

Responders who have had a change in dose after the Decision Point, or patients who were 
rescued to baricitinib at Week 36, will not be eligible for randomized withdrawal and will 
remain in their same treatment group.  

Eligible patients will be automatically randomized in a blinded manner by the IWRS in a 
3:1 ratio to either stay on their current dose of baricitinib or transition to placebo 
(randomized withdrawal).  

Any patients in the placebo treatment arm at Week 52 who have achieved a SALT ≤20 
will remain on placebo.

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
Responders who experience a loss of treatment response after Week 52 (defined as 
>20-point absolute worsening in total SALT score), and who:
o
were randomized to placebo at Week 52 (randomized withdrawal), will be 
automatically retreated with their baricitinib dose, as randomized at Baseline 
(Visit 2).
o
remained on baricitinib at Week 52 (randomized withdrawal), will continue to 
receive the same dose of baricitinib.
o
were randomized to placebo at Baseline (Visit 2), will remain on placebo. 
Note:  An unscheduled visit after Week 52 may be used to assess the patient who reports a loss 
of treatment response. 
Nonresponders (SALT >20)

Patients who have been in the baricitinib 4-mg treatment group from Baseline AND have 
never achieved a SALT ≤20 by Week 52 AND do not have a ≥2-point improvement from 
Baseline in clinician-reported outcome (ClinRO) measure for eyebrow or eyelash hair 
loss at Week 52 will be automatically transitioned to placebo.

Patients who have been in the baricitinib 4-mg treatment group and have achieved a 
SALT ≤20 before Week 52 and have lost response, will remain on baricitinib 4-mg.

Those who have been in the baricitinib 2-mg treatment group from Baseline will be 
rescued to baricitinib 4-mg.

Those who were transitioned to baricitinib 4-mg after the Decision Point, or were rescued 
to baricitinib at Week 36, will continue in their current treatment arm at Week 52.
At Week 76

Patients who are nonresponders, SALT >20, at Weeks 52 AND 76 will be automatically 
discontinued from the study at Week 76, unless they have a ≥2-point improvement from 
Baseline in ClinRO measure for eyebrow or eyelash hair loss.
Statistical Analysis:
Analysis to select up to 2 doses to advance to Stage 2 of the trial or stop the trial for futility will 
be conducted in the Phase 2, Week 12 Interim Analysis Set (IAS), which includes the first 
approximately 100 randomized and treated patients in Stage 1 who complete the Visit 5 
(Week 12) assessment or discontinue early.  A 2nd interim analysis will be conducted when all 
Phase 2 patients have completed 36 weeks of treatment or discontinued early and this efficacy 
analysis will use the Phase 2, Week 36 IAS. Unless otherwise specified, the efficacy and health 
outcome analyses during the Phase 3 portion of the study will be conducted on the Full Analysis 
Set (FAS), which includes all patients enrolled in Phase 3 portion and randomized to baricitinib 
4-mg, baricitinib 2-mg, and placebo treatment arms in both Stages 1 and 2. Safety analyses will 
be conducted in safety population.  Additional efficacy or safety interim analyses prior to the 
final database lock (F-DBL) may occur to support regulatory submissions and scientific 
disclosures and will be described in detail in the SAP.

I4V-MC-JAHO(e) Clinical Protocol
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Treatment comparisons of discrete efficacy variables will be made using a logistic regression 
analysis as primary analysis with geographic region, duration of current episode at Baseline
(<4 years vs ≥4 years), baseline value, and treatment group in the model unless, otherwise, 
stated.  In the case when logistic regression model does not produce statistical results due to 
sparse data, Fisher exact test will be used. The proportions and 95% confidence intervals (CIs) 
will be reported.  Patients will be generally considered nonresponders for the nonresponder 
imputation- (NRI-) based analysis if they do not meet clinical response criteria or if they 
discontinued study or study treatment at any time prior to the timepoint of interest for any reason.  
Additional analyses may be performed and will be described in detail in the statistical analysis 
plan (SAP) for patients who discontinued the study and for patients missing measurements prior 
to a fixed timepoint. 
Treatment comparisons of continuous efficacy and health outcome variables will be made using 
analysis of covariance (ANCOVA) with geographic region, duration of current episode at 
Baseline (<4 years vs ≥4 years), treatment group, and baseline value in the model unless 
otherwise stated.  Type III tests for least square (LS) means will be used for the statistical 
comparison between treatment groups.  The LS mean difference, standard error, p-value, and 
95% CI will also be reported.  Additional analyses may be performed and will be described in 
detail in the SAP.  
Time-to-event analysis will be done and analyzed using log-rank test. A Cox proportional 
hazards model may be used with treatment and other stratification variables in the model unless 
otherwise stated.  Hazard ratio with CIs may be reported.  Kaplan–Meier curves will also be 
produced.  Diagnostic tests for checking the validity of the proportional hazards assumption may
be performed and these would be described in detail in the SAP.  If the assumption of 
proportional hazards is not justified, nonproportionality may be modeled by stratification.
Fisher exact test will be used for all adverse events (AEs), discontinuation, and other categorical 
safety data.  Continuous vital signs and laboratory values will be analyzed by an ANCOVA with 
treatment and baseline values in the model.  

I4V-MC-JAHO(e) Clinical Protocol
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2. Schedule of Activities
The Schedule of Activities described below should be followed for all participants enrolled in
Study JAHO. In the event participation in this study is affected by exceptional circumstances
(such as pandemics or natural disasters), please refer to Appendix 8 and consult with the
sponsor’s representative for additional guidance.

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Table JAHO.1.
Schedule of Activities
Screen-
ing
Double-blind Treatment 
Period
Long-term Extension
Bridging Extension
PTFU
Period 
1
Period 2 (36 weeks)
Period 3 (68 weeks)
Period 4 (96 weeks)
Period 
5
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18 
19
20
21
22
23
24/
ET
UVa
801
Weeks from 
Randomization
0
4
8
1
2
16
24
36
40
44
52
56
60
64
68
76
88
104
120
136
152
168
184
200
Period2 
to 4
Visit tolerance 
interval (days)
-3 to -
35
±
4
±
4
±
4
±4
±7
±7
±4
±4
±7
±4
±4
±4
±4
±7
±7
±7
±10
±10
±10
±10
±10
±10
28 ±4
Inclusion and 
Exclusion 
Review 
X
X
Informed 
consent
X
Randomization
X
Xb
Xb
Clinical 
Assessments
Demographics 
X
Preexisting 
Conditions/Medi
cal History
X
MPHL/FPHL 
History
X
Substance Use 
(alcohol, 
tobacco)
X
Previous and 
Current AA 
Treatments
X
Chest x-ray
(posterior-
anterior view)c
X
TB testd
X
Read PPD if 
applicable 
(48 to 72 hours 
after V1)e
X
Physical 
X

I4V-MC-JAHO(e) Clinical Protocol
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Screen-
ing
Double-blind Treatment 
Period
Long-term Extension
Bridging Extension
PTFU
Period 
1
Period 2 (36 weeks)
Period 3 (68 weeks)
Period 4 (96 weeks)
Period 
5
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18 
19
20
21
22
23
24/
ET
UVa
801
Weeks from 
Randomization
0
4
8
1
2
16
24
36
40
44
52
56
60
64
68
76
88
104
120
136
152
168
184
200
Period2 
to 4
Visit tolerance 
interval (days)
-3 to -
35
±
4
±
4
±
4
±4
±7
±7
±4
±4
±7
±4
±4
±4
±4
±7
±7
±7
±10
±10
±10
±10
±10
±10
28 ±4
Examination
12-lead ECG 
(single, local)
X
Height 
X
Weight
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BMI
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
X
X
Symptom-
directed Physical 
Examf
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
MPHL/FPHL 
Assessmentg
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
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
X
X
X
IWRS
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Photography 
(4 planes of 
scalp and 1 
frontal view of 
face and scalp)h
X
X
X
X
Xh
Photography 
Eyebrows/
Eyelashesh
X
X
X
X
Xh
Photography 
Nails (if 
involvement)h
X
X
X
X
Xh
IP dispensed
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IP returned and 
compliance 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAHO(e) Clinical Protocol
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LY3009104
Screen-
ing
Double-blind Treatment 
Period
Long-term Extension
Bridging Extension
PTFU
Period 
1
Period 2 (36 weeks)
Period 3 (68 weeks)
Period 4 (96 weeks)
Period 
5
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18 
19
20
21
22
23
24/
ET
UVa
801
Weeks from 
Randomization
0
4
8
1
2
16
24
36
40
44
52
56
60
64
68
76
88
104
120
136
152
168
184
200
Period2 
to 4
Visit tolerance 
interval (days)
-3 to -
35
±
4
±
4
±
4
±4
±7
±7
±4
±4
±7
±4
±4
±4
±4
±7
±7
±7
±10
±10
±10
±10
±10
±10
28 ±4
assessed 
Scales/
Questionnaires
SALT (AA-
IGA)i
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hamilton-
Norwood Scaleg
X
X
X
X
X
ClinRO Measure 
for Eyebrow 
Hair Loss
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ClinRO Measure 
for Eyelash Hair 
Loss
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ClinRO Measure 
for Nail 
Appearance
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO for Scalp 
Hair Assessment
X 
(Stage 2 
only)
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO Measure 
for Eyebrows
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO Measure 
for Eyelashes 
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO Measure 
for Eye Irritation 
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO Measure 
for Nail 
Appearance 
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
EQ-5D-5L
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
X
X
X
Skindex-16 
Adapted for AA 
(Stage 2 only)
X
X
X
X
X
X
X
X
X
X

I4V-MC-JAHO(e) Clinical Protocol
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Screen-
ing
Double-blind Treatment 
Period
Long-term Extension
Bridging Extension
PTFU
Period 
1
Period 2 (36 weeks)
Period 3 (68 weeks)
Period 4 (96 weeks)
Period 
5
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18 
19
20
21
22
23
24/
ET
UVa
801
Weeks from 
Randomization
0
4
8
1
2
16
24
36
40
44
52
56
60
64
68
76
88
104
120
136
152
168
184
200
Period2 
to 4
Visit tolerance 
interval (days)
-3 to -
35
±
4
±
4
±
4
±4
±7
±7
±4
±4
±7
±4
±4
±4
±4
±7
±7
±7
±10
±10
±10
±10
±10
±10
28 ±4
HADS
X
X
X
X
X
X
X
X
X
X
C-SSRS and 
Self-Harm 
Supplementj
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm 
Follow-up 
Formk
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory 
Assessment
Lipids (Fasting 
Visit)l
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical 
Chemistrym
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hematology
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum 
Pregnancy Testn
X
FSHo
X
TSH
X
HIV
X
HCV antibody 
testingp
X
HBV testingq
X
HBV DNAq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine Pregnancy 
Testn
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacogenetic
s:  blood
X
Serum 
immunoglobulin 
X
X
X
X

I4V-MC-JAHO(e) Clinical Protocol
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Screen-
ing
Double-blind Treatment 
Period
Long-term Extension
Bridging Extension
PTFU
Period 
1
Period 2 (36 weeks)
Period 3 (68 weeks)
Period 4 (96 weeks)
Period 
5
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18 
19
20
21
22
23
24/
ET
UVa
801
Weeks from 
Randomization
0
4
8
1
2
16
24
36
40
44
52
56
60
64
68
76
88
104
120
136
152
168
184
200
Period2 
to 4
Visit tolerance 
interval (days)
-3 to -
35
±
4
±
4
±
4
±4
±7
±7
±4
±4
±7
±4
±4
±4
±4
±7
±7
±7
±10
±10
±10
±10
±10
±10
28 ±4
(IgE)
Exploratory 
storage samples 
(serum, plasma)
X
X
X
X
X
X
X
X
X
X
RNA and 
biomarkers:  
blood
X
X
X
X
X
X
X
X
X
X
Baricitinib 
plasma 
concentration 
(PK sample)r
X X
X
X
X
Xr
Abbreviations:  AA = alopecia areata; AA-IGA = Alopecia Areata Investigator Global Assessment; AGA = androgenetic alopecia; BMI = body mass index; 
BP = blood pressure; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; ClinRO = clinician-reported outcome; C-SSRS = Columbia Suicide 
Severity Rating Scale; DNA = deoxyribonucleic acid; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EQ-5D-5L = European Quality 
of Life – 5 Dimensions – 5 Level; ET = early termination; FPHL = female pattern hair loss; FSH = follicle-stimulating hormone; HBcAb = hepatitis B core 
antibody; HBsAb = hepatitis B surface antibody; HADS = Hospital Anxiety and Depression Scale; HBV = hepatitis B virus; HCV = hepatitis C virus; 
HIV = human immunodeficiency virus; IgE = immunoglobulin E; IP = investigational product; IWRS = investigator web response system; MPHL = male 
pattern hair loss; PK = pharmacokinetic; PPD = purified protein derivative; PRO = patient-reported outcome; PTFU = posttreatment follow-up; 
RNA = ribonucleic acid; SALT = Severity of Alopecia Tool; SF-36 = Short Form-36 Health Survey acute version 2; TB = tuberculosis; TSH = thyroid-
stimulating hormone; UV = unscheduled visit; V = Visit.
a
Only applicable to patients enrolled during Stage 1, who will need an unscheduled visit(s) after the Decision Point to potentially transition to baricitinib 4-mg
(SALT assessment not required) and to patients who experience a loss of treatment benefit after Week 52 if no scheduled visit available (SALT assessment 
required to confirm loss of treatment benefit) (see Sections 5.1.2 and 5.1.6).  Not applicable to unscheduled visits conducted for other reasons.
b
At Week 36, nonresponders (SALT >20) in the placebo treatment arm will be rescued to baricitinib (see Section 5.1.6 for details).  For details on responder 
randomization at Week 52, refer to Section 5.1.6.
c
A posterior–anterior view chest x-ray will be obtained locally at Screening (Visit 1), unless one has been performed in the past 6 months and the x-ray and/or 
the report is available.
d
TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®.  See Exclusion Criterion [27] for description of TB testing.  In countries where the 
QuantiFERON-TB Gold test or T-SPOT is available, either test may be used instead of the PPD TB test.  It is preferred that the QuantiFERON-TB Gold test 

I4V-MC-JAHO(e) Clinical Protocol
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be performed centrally; the T-SPOT must be performed locally.  Note:  Patients with a history of active or latent TB who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was completed, and have a screening chest x-ray with no evidence of active TB 
may be enrolled if other entry criteria are met.  Such patients would not be required to undergo the protocol-specific TB testing, but must have a chest x-ray at 
screening.
e
If PPD testing was chosen to test for TB, then the patient must return and have the PPD test read 48 to 72 hours after Visit 1 (post-PPD).
f
The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints.
g
Presence of MPHL (AGA) will be assessed at screening using the Hamilton-Norwood Scales for male patients, through examination, and via patient 
interview; these will be re-evaluated at Weeks 36, 52, 104, and 200/ET.  Presence of FPHL (AGA) will be assessed at Weeks 36, 52, 104, and 200/ET for 
female patients whose history of AGA is “no history” or unknown at screening.
h
All sites/patients will obtain photographs of the scalp and eyebrows/eyelashes at Baseline.  Photographs of the nails will be obtained only from patients with 
nail involvement (ClinRO ≥1) at Baseline.  All sites/patients will obtain photographs of the scalp at Weeks 12, 36, and 52, and at Early Termination if it 
occurs before Visit 11 (Week 52).  Photographs of the eyelash/eyebrows and/or nails will be captured at Weeks 12, 36, and 52 only from patients with AA 
involvement of those areas (ClinRO ≥1) at Baseline (Visit 2).  See Section 9.1.4 for details. 
i
AA-IGA will be automatically derived from the SALT scores.
j
A “Baseline/Screening” form is used at Visit 1. A “Since Last Visit” form used for all remaining visits.  A suicidal ideation and behavior subscales excerpt is
adapted for the assessment of 11 preferred ideation and behavior categories.
k
The Self-Harm Follow-Up Form is only required if triggered by the Self-Harm Supplement Form
l
Fasting lipid profile:  patients should not eat or drink anything except water for 8 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. For ET 
visits, collect fasting lipids when possible.
m Clinical chemistry will include the following value calculated from serum creatinine:  eGFR (calculated using the CKD-EPI creatinine 2009 equation).
n
For all women of childbearing potential, a serum pregnancy test (central laboratory) will be performed at Visit 1.  Urine pregnancy tests (local laboratory) will 
be performed at Visit 2 and at all subsequent study visits.  If required per local regulations and/or institutional guidelines, pregnancy testing can occur at other 
times during the study treatment period.
o
For female patients ≥40 and <60 years of age who have had a cessation of menses for at least 12 months, an FSH test will be performed to confirm 
nonchildbearing potential (FSH ≥40 mIU/mL).
p
For patients who are positive for HCV antibody, a follow-up test for HCV RNA will be performed automatically.  Patients who are positive for HCV antibody 
and negative for HCV RNA may be enrolled.
q
Patients who are positive for HBcAb and negative for HBV DNA may be enrolled.  Any enrolled patient who is HBcAb positive, regardless of HBsAb status 
or level, must undergo HBV DNA testing per the schedule.
r
Samples for the other clinical laboratory assessments must be drawn prior to receiving the first dose.  PK samples are required at ET Visit only if the patient 
discontinues the study prior to Visit 6/Week 16.  See Section 9.5 for PK details when IP should be taken in relationship to PK sampling and timing of PK 
sampling.

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3. Introduction
3.1.
Study Rationale
Although, in the past, alopecia areata (AA) has been considered by some to be a benign 
condition, severe AA is now recognized as a significant medical condition with emotional and 
psychosocial distress, including high prevalence of depression and anxiety (Colon et al. 1991; 
Hunt and McHale 2005; Villasante Fricke and Miteva 2015).  Additionally, reduction in health-
related quality of life experienced by patients with AA has been well documented (Jankovic et al.
2016; Liu et al. 2016; Rencz et al. 2016). Alopecia areata can be reversible – either 
spontaneously or after various types of treatments, but results are inconsistent (Islam et al. 2015)
and there is currently no Food and Drug Administration- (FDA-) approved treatment for AA. 
Baricitinib is an orally available, selective inhibitor of Janus kinases (JAKs). 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 tyrosine kinase 2 (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 and JAK2 and less potency for JAK3 or TYK2 (Fridman et al. 2010).  
Dual inhibition of JAK1 and JAK2, which may interrupt interferon gamma (IFNsignaling and 
other inflammatory pathways that contribute to the immunopathogenesis of AA, and clinical 
evidence with other JAK inhibitors support the investigation of baricitinib in the treatment of 
AA. This adaptive, operationally seamless, Phase 2/3, placebo-controlled study is designed to 
select up to 2 doses of baricitinib and assess their efficacy and safety for the treatment of severe 
(Severity of Alopecia Tool [SALT] score of 50% to 94%) and very severe AA (SALT score of 
95% to 100%).  Additionally, it will include a randomized withdrawal to explore the persistence 
of treatment effects and efficacy of retreatment upon relapse.  This operationally seamless design 
will provide longer-term safety data earlier in the clinical development program, compared to 
running separate Phase 2 and Phase 3 studies.
Lilly has initiated a clinical program to evaluate the efficacy and safety of baricitinib in adult 
patients with severe (SALT score of 50% to 94%) and very severe AA (SALT score of 95% to 
100%) AA of the scalp.
This clinical program currently comprises 2 trials:

Study JAHO described in this protocol, is a double-blind, placebo-controlled adaptive 
Phase 2b/3 trial. In the Phase 2 dose-ranging portion of the study, 3 dose regimens were 
tested: baricitinib 1-mg QD, baricitinib 2-mg QD, and baricitinib 4-mg QD.  The results 
of the interim analysis of the Phase 2 portion confirmed the potential of baricitinib to 
restore hair growth and supported further evaluation of the 2-mg QD and 4-mg QD 
regimen in the Phase 3 portion of the study.  See Section 5.5 (Justification for Dose) for 
more information.

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
Study I4V-MC-JAIR (JAIR), is also a double-blind, placebo-controlled Phase 3 trial and 
will evaluate the same doses.
Studies JAHO and JAIR have identical inclusion and exclusion criteria and have the same design 
and primary and key secondary objectives for the 36-week, double-blinded, placebo-controlled 
Treatment Period (Period 2).
3.2.
Background
Alopecia areata is an autoimmune disease usually characterized by patches of nonscarring hair 
loss that can affect the scalp, face, and body, with a lifetime prevalence of approximately 2% 
(Wasserman et al. 2007; Islam et al. 2015; Korta et al. 2018).  The extent of hair loss in this 
condition can vary, including total hair loss on the scalp and loss of facial and/or other body hair 
(Islam et al. 2015).  Alopecia areata can affect children, adolescents, and adults (Hordinsky and 
Donati 2014).  
Alopecia areata is one of the more common autoimmune diseases and its visible phenotypic 
characteristic hair loss and lack of FDA-approved treatments provide a unique opportunity for 
novel treatment approaches with a drug with immune modulatory effects such as baricitinib.  
Clinical manifestations of AA (hair loss and nail effects) may be constant or sporadic and can 
affect different areas of the scalp, face, or body at different times during life, or cause hair loss in 
the entire scalp or the entire body at once (Olsen 2011).  As an autoimmune disease in which the 
patient’s own T cells produce cytokines that inhibit hair follicle growth, AA may present as 
patchy AA, with partial hair loss in one or multiple well-circumscribed round patches in the 
scalp (or other hair-bearing site), or it can progress to hair loss involving the entire scalp 
(alopecia totalis [AT]), or extend to complete hair loss of head and body (alopecia universalis 
[AU]) (Olsen 1999; Olsen et al. 2004).  Patchy alopecia, AT, and AU are considered part of the 
clinical spectrum of the same disease (Hordinsky and Junqueira 2015).  Alopecia areata can 
cause significant emotional and psychosocial distress (Hunt and McHale 2005).  A 66% to 74% 
lifetime prevalence of psychiatric disorders has been reported in patients with AA, with a 38% to 
39% lifetime prevalence of depression and a 39% to 62% prevalence of generalized anxiety 
disorder (Colon et al. 1991; Villasante Fricke and Miteva 2015).  Quality of life is also 
consistently diminished in patients with AA (Jankovic et al. 2016; Liu et al. 2016; Rencz et al. 
2016).  The Global Burden of Disease Study (GBD) determined the burden of AA to be a mean 
of 19.4 years of healthy life lost (Karimkhani et al. 2015).  However, this GBD study did not 
account for other potential harms, such as emotional distress and financial impact (Karimkhani et 
al. 2015).
Insights into the immunopathogenesis of AA began with the recognition of the hair follicle as being 
an immune-privileged site like the eye and testes (Paus et al. 2005).  Next, disruption of this immune 
privilege occurs upon follicular influx by auto-reactive CD8+ T cells, leading to increases in major 
histocompatibility complex (MHC) class I and II antigens and inflammation disrupting hair follicle 
biology (Islam et al. 2015; Strazzulla et al. 2018).  Activation of the pathogenic T cells leads to IFN
production which contributes both to enhanced MHC class I and II antigens and interleukin-15 
(IL-15) (Islam et al. 2015; Strazzulla et al. 2018) accompanied by additional cytokines including 

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IL-2, IL-13, IL-23, and thymic stromal lymphopoietin (Suárez-Fariñas et al. 2015).  All of these 
inflammatory-related cytokines are dependent on JAK/STAT signaling, and of particular note 
IFNutilizes JAK1 and JAK2.  Animal models support the theory of AA in which autoreactive 
T cells (NKG2D+) drive the hair loss by increasing IFNand inflammatory gene expression 
signatures as noted above, which could be reversed using JAK inhibition in mice (Xing et al. 
2014).  
There are currently no FDA-approved treatments for AA.  While not all patients with AA are 
likely to require treatment because AA is often mild and intermittent (Tan et al. 2002; 
Wasserman et al. 2007), for patients with severe and persistent disease, safe and efficacious 
treatments are lacking. Use of a JAK 1/JAK 2 inhibitor such as baricitinib may be able to 
reinitiate production of mature terminally differentiated follicles at sites of prior inflammation.  
3.3.
Benefit/Risk Assessment
Several retrospective case series, case reports, and open-label studies have been published 
describing positive outcomes in patients with severe (SALT score of 50% to 94%) or very severe 
AA (SALT score of 95% to 100%), treated with different JAK inhibitors for 4 to 18 months. In 
these reports, more than one-half of patients experienced hair regrowth of 50% or more after 
beginning treatment with a JAK inhibitor (Xing et al. 2014; Mackay-Wiggan et al. 2016; 
Craiglow et al. 2017; Liu et al. 2017; Jabbari et al. 2018; Liu et al. 2018;), including baricitinib
(Jabbari et al. 2015).  A 66-patient, open-label study reported that approximately one-third of 
patients achieved hair regrowth of >50% after treatment with tofacitinib; however, these patients 
were treated with a JAK inhibitor for only 3 months (Kennedy Crispin et al. 2016). Results from 
the interim analysis of the Phase 2 portion of Study JAHO showed that the 2-mg and 4-mg 
baricitinib doses demonstrated numerical superiority over the 1-mg dose and placebo, in hair 
regrowth, after 12 (SALT30) and 16 (SALT50) weeks of treatment with no new safety signal.  
These results have been confirmed by a second interim analysis of Phase 2 portion of Study 
JAHO where the 2-mg dose and 4-mg dose were statistically significantly superior to placebo on 
the primary endpoint (SALT≤20) after 36 weeks of treatment. 
Serious infections, venous thromboembolic events (VTEs), hepatotoxicity, and fetal 
malformations were identified as important potential risks with baricitinib in RA studies  
Although infections were seen in approximately one-half of the study population exposed to 
baricitinib in the RA program, only 3.6% of patients reported a serious treatment-emergent 
infection, and rates were similar in both baricitinib- and placebo-treated patients.  In the Phase 2 
atopic dermatitis (AD) study, approximately 25% of patients treated with the 4-mg dose 
experienced a treatment-emergent adverse events (TEAE) of infection and infestation, compared 
to 20% of patients treated with placebo.  There were no serious infections, opportunistic 
infections, or herpes zoster infections reported during the treatment period in the AD Phase 2 
study.  There was no serious event reported at the time of the second interim analysis of the 
Phase 2 portion of Study JAHO after 36 weeks of treatment. The nonserious infections for 
baricitinib noted in the RA program (upper respiratory tract infections, herpes zoster, herpes 
simplex) are readily diagnosed and manageable, and typically resolve without long-term 
sequelae.  It is recommended that, where indicated, herpes zoster vaccination will be offered to 

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patients before receiving baricitinib; herpes zoster infections, when they have occurred, have 
generally been mild-to-moderate, localized, and without long-term problems. Exclusion criteria 
have been added to the protocol to limit enrollment of patients who are at increased risk for
infection.  
Cases of hepatotoxicity have not been identified with baricitinib use, but increases in alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL) have been 
seen in RA patients.  Most of these increases improved with continued use or temporary 
discontinuation of baricitinib with no long-term effects.  Exclusion criteria to not enroll patients 
with liver failure or increased liver analytes, appropriate monitoring of hepatic analytes, and 
discontinuation criteria have been included in the protocol.  
In toxicology studies, fetal malformations were reported at doses higher than what is used in 
human patients.  Only a small number of patients have become pregnant in baricitinib clinical 
trials, and there have been no reports of fetal malformations in these pregnancies.  In current 
study protocols, pregnant patients are excluded from entry, contraceptive use is defined in the 
inclusion criteria, and patients who become pregnant are discontinued from the trial.
Venous thromboembolic events have been determined to be an important potential risk for 
baricitinib. There was a numerical imbalance in reports of VTEs in the 24-week, placebo-
controlled period of the Phase 3 trials of patients with RA.  Available evidence does not establish 
a causal association.  The exposure-adjusted incidence rate of VTE for baricitinib-treated RA 
patients over long-term exposures was similar to the background rates published in the literature 
for the target population (i.e., RA).  There was no pattern of increased or decreased risk during
long-term exposures, and cases observed with baricitinib were confounded by 1 or more 
recognized risk factors for a VTE (eg, history of VTE, increased body mass index [BMI], older 
age). Venous thromboembolic event risk can be managed through risk mitigation strategies.  
Exclusion and discontinuation criteria have been added to the protocol to limit participation of 
patients who are at increased risk for VTE. Patients will be excluded if they have a previous 
history of a VTE, or have a combination of 2 or more risk factors for a VTE (eg, increased BMI, 
older age, combination use of oral contraceptive with smoking).  History of a previous VTE is 
the strongest risk factor for development of a second VTE, and the existing exclusion criteria for 
patients with previous history of a VTE will also serve to exclude patients with other risk factors.
Presymptomatic screening for hypercoagulable conditions is not currently recommended, even in 
the prescribing information for medications with known increased risk for VTEs.  Although 
temporary interruption of investigational product (IP) is not a requirement at times of increased 
potential risk for VTE (eg, surgery, significant air travel, or other situations involving prolonged 
immobilization), we recommend following appropriate VTE prophylaxis guidelines to help 
manage the VTE risk under these circumstances.
There was no VTE reported at the time of the second interim analysis of the Phase 2 portion of 
Study JAHO after 36 weeks of treatment.
Therefore, in the context of the cumulative knowledge, the benefit/risk balance for baricitinib for 
the treatment of adult patients with severe AA is assessed to be favorable.

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More detailed 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 JAHO.2 shows the objectives and endpoints of the study.
Table JAHO.2.
Objectives
Objectives
Endpoints
Primary Objective 
To test the hypothesis that the 4-mg dose or 2-mg dose
of baricitinib is superior to placebo in the treatment of 
patients with severe or very severe AA

Proportion of patients achieving SALT ≤20 at 
Week 36.
Key Secondary Objectives (Double–Blind, Placebo-Controlled Treatment Period)
These are pre-specified objectives that will be adjusted for multiplicity.
To compare the efficacy of baricitinib 4-mg or 2-mg to 
placebo in AA during the double-blind, placebo-
controlled treatment period as measured by physician-
assessed signs and symptoms of AA

Proportion of patients achieving SALT ≤20 at 
Weeks 16 and 24.

Percent change from baseline in SALT score at 
Week 36.

Proportion of patients achieving a SALT50at 
Week 12.  

Proportion of patients achieving a SALT90 at 
Week 36.

Proportion of patients achieving an absolute 
SALT ≤10 at Weeks 24 and 36.

Proportion of patients achieving ClinRO Measure 
for EB Hair Loss 0 or 1 with ≥2-point 
improvement from Baseline at Week 36 (among 
patients with ClinRO Measure for EB Hair Loss ≥2 
at Baseline).

Proportion of patients achieving ClinRO Measure 
for EL Hair Loss 0 or 1 with ≥2-point improvement 
from Baseline at Week 36 (among patients with 
ClinRO Measure for EL Hair Loss ≥2 at Baseline).
To compare the efficacy of baricitinib 4-mg or 2-mg to 
placebo in AA during the double-blind, placebo-
controlled treatment period as assessed by a PRO
measure

Proportion of patients with PRO for Scalp Hair 
Assessment score of 0 or 1 with a ≥2-point 
improvement from Baseline at Week 36 among 
patients with a score of ≥3 at Baseline.
Other Secondary Objectives (Double–Blind, Placebo-Controlled Treatment Period)
These are pre-specified objectives that will NOT be adjusted for multiplicity.
To compare the efficacy of baricitinib 4-mg or 2-mg to 
placebo in AA during the double-blind, placebo-
controlled treatment period as measured by physician-
assessed signs and symptoms of AA

Proportion of patients achieving SALT50 at 
Weeks 16, 24, and 36.

Proportion of patients achieving a SALT75 at 
Weeks 24 and 36.

Proportion of patients achieving a SALT90 at 
Week 24.

Change from Baseline in SALT score at Weeks 12, 
16, 24, and 36. 

Percent change from Baseline in SALT score at 
Weeks 12, 16, and 24.

Time to achieve SALT ≤20.

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Objectives
Endpoints

Proportion of patients achieving SALT100 at 
Weeks 24 and 36.

Proportion of patients achieving ClinRO Measure 
for EB Hair Loss 0 or 1 with ≥2-point 
improvement from baseline at Weeks 16 and 24 
(among patients with ClinRO Measure for EB Hair 
Loss ≥2 at Baseline).

Proportion of patients achieving ClinRO Measure 
for EL Hair Loss 0 or 1 with ≥2-point improvement 
from baseline at Weeks 16 and 24 (among patients 
with ClinRO Measure for EL Hair Loss ≥2 at 
Baseline).
To compare the efficacy of baricitinib 4-mg or 2-mg to 
placebo in AA during the double-blind, placebo-
controlled treatment period as assessed by PRO
measures and quality of life tools

Proportion of patients with PRO for Scalp Hair 
Assessment score of 0 or 1 with a ≥2-point 
improvement from Baseline at Weeks 12 and 24
among patients with a score of ≥3 at Baseline

Proportion of patients achieving PRO Measure for 
EB 0 or 1 with ≥2-point improvement from 
baseline at Weeks 16, 24, and 36 (among patients 
with PRO Measure for EB ≥2 at Baseline).

Proportion of patients achieving PRO Measure for 
EL 0 or 1 with ≥2-point improvement from 
baseline at Weeks 16, 24, and 36 (among patients 
with PRO Measure for EL ≥2 at Baseline)

Mean change from Baseline in HADS-A and 
HADS-D total scores at Weeks 24 and 36
Other Secondary (Patients entering Randomized Withdrawal)
These are pre-specified objectives that will NOT be adjusted for multiplicity.
To compare the maintenance of efficacy for patients 
randomized to remain on baricitinib, compared with 
patients randomized to placebo at Week 52 of the 
long-term extension period, as measured by physician-
assessed signs of AA

Proportion of patients maintaining SALT ≤20 at 
Weeks 64, 76, 88, 104, 120, 136, 152, 168, 184, 
and 200.

Proportion of patients experiencing a loss of 
treatment benefit (>20-point absolute worsening in 
SALT score) at Weeks 64, 76, 88, 104, 120, 136, 
152, 168, 184, and 200.

Time to loss of treatment benefit (>20-point 
absolute worsening in SALT score).
For patients experiencing loss of treatment benefit after 
randomization to placebo at Week 52:

To evaluate the recapture of efficacy for patients 
who were retreated after experiencing a loss of 
treatment benefit during the long-term maintenance 
period as measured by physician-assessed signs of 
AA

Proportion of patients that achieve a SALT ≤20 at
12, 16, 24, and 36 weeks of retreatment with 
baricitinib.

Percent change in SALT score at 12, 16, 24, and 
36 weeks of retreatment with baricitinib.

To evaluate the recapture of efficacy for patients 
who were retreated after experiencing a loss of 
treatment benefit during the long-term maintenance 
period as assessed by PRO and quality of life tools

Proportion of patients with a PRO for Scalp Hair 
Assessment score of 0 or 1 at 12, 16, 24, and 36 
weeks of retreatment with baricitinib.

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Objectives
Endpoints
Exploratory Objectives may include evaluating the response to baricitinib treatment regimens on clinical measures 
and patient-reported outcomes.  These endpoints may include dichotomous endpoints or change from baseline for 
the following measures:  SALT, AA-IGA, SALT30, ClinROs for Nail Appearance, Eyebrows, and/or Eyelash Hair 
Loss, PROs for Scalp Hair Assessment, Eyebrows, and Eyelashes, Nail Appearance and Eye Irritation, Skindex-16
AA, SF-36, EQ-5D-5L, HADS.  Assessments of efficacy may be performed beyond Week 104 up to Week 200.  In 
addition, baricitinib pharmacokinetics will be characterized in the AA population and relationships between 
exposure and study endpoints will be explored.  
Abbreviations:  AA = alopecia areata; AA-IGA = Alopecia Areata Investigator Global Assessment; 
ClinRO = clinician-reported outcome; EB = eyebrow; EL = eyelash; EQ-5D-5L= European Quality of Life –
5 Dimensions – 5 Level; HADS = Hospital Anxiety and Depression Scale; PRO = patient-reported outcome; 
SALT = Severity of Alopecia Tool; SALT30 = at least 30% improvement from Baseline in SALT score; 
SALT50 = at least 50% improvement from Baseline in SALT score; SALT75 = at least 75% improvement from 
Baseline in SALT score; SALT90 = at least 90% improvement from Baseline in SALT score; SALT100 = 100% 
improvement from Baseline in SALT score; SF-36 = Short Form-36 Health Survey acute version 2; Skindex-16 
AA = Skindex-16 Adapted for Alopecia Areata.

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5. Study Design 
5.1. Overall Design 
Study I4V-MC-JAHO (JAHO) is an adaptive, operationally seamless, Phase 2/3, multicenter, 
randomized, double-blind, placebo-controlled, parallel-group, outpatient study designed to 
identify up to 2 doses of baricitinib to be evaluated further in the Phase 3 portion of the study.  
The 2-mg and 4-mg doses of baricitinib were selected as a result of the Phase 2 interim analysis; 
therefore, efficacy and safety of baricitinib 2-mg and 4-mg will be compared to placebo in adult 
patients with severe (SALT score of 50% to 94%) or very severe (SALT score of 95% to 100%) 
scalp AA during the Phase 3 portion of Study JAHO.  Approximately 725 adult patients will be 
enrolled into Study JAHO.  Approximately 100 patients will be enrolled into the Phase 2 portion 
of the study and approximately 625 patients will be enrolled into the Phase 3 portion of the 
study. 
Patients must have a current AA episode of more than 6 months’ duration prior to screening 
(Visit 1), with at least 50% scalp involvement at screening AND Baseline (Visits 1 and 2) with 
no spontaneous improvement (no more than a 10 point reduction in SALT) over the past 6 
months.  Patients with a current episode of severe or very severe AA of more than 8 years will 
not be eligible for inclusion in the study unless episodes of regrowth, spontaneous or under 
treatment, have been observed on the affected areas of the scalp over the past 8 years.   
All procedures to be conducted during the study, including timing of all procedures, are indicated 
in the Schedule of Activities (SOA) (Section 2).  Section 9.4.4 describes collection of laboratory 
samples; Appendix 2, Appendix 4, and Appendix 5 list the specific laboratory tests that will be 
performed for this study.  Study governance considerations are described in detail in Appendix 3.  
Section 10.3.7 outlines information regarding the interim analyses and Decision Point 
Committee.  
Study Stages 
The enrollment of patients in the study will be divided into 2 stages, which are separated by the 
Decision Point.  Different randomization schemes at Baseline (Visit 2) will be used by the 
interactive web-response system (IWRS) (during Stage 1 [Phase 2], Stage 1 [Phase 3] and Stage 2 
[see Figure JAHO.1]). 
 Stage 1:  the time from study start until the Decision Point.  A maximum of 
approximately 300 patients will be randomized during Stage 1, before the Decision Point.  
See Section 5.1.1 for additional details.  
 Decision Point:  the point in time when up to 2 baricitinib doses will be selected to 
continue in Stage 2 or the study will be stopped for futility based on the outcome of the 
interim analysis.  See Section 5.1.2 for additional detail.  
 Stage 2:  the time after the Decision Point until the end of the study during which the 
remaining patients (approximately 425 patients) will be enrolled into the Phase 3 portion 
of the study.  See Section 5.1.3 for additional detail.  

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
Based on the Week 12 interim analysis of the Phase 2 population of this study, baricitinib
2-mg QD (low dose) and baricitinib 4-mg QD (high dose) were selected at Decision Point 
to continue into Stage 2 of Study JAHO.
Abbreviations:  eGFR = estimated glomerular filtration rate; PBO = placebo; QD = once daily administration; V = 
visit; WO = washout.
a
Patients randomized during Stage 1 who are in the treatment arm that is discontinued (baricitinib 1-mg) will be 
transitioned to the 4-mg dose of baricitinib remaining in the study after the Decision Point. 
b
The maximal baricitinib dose for patients with renal impairment (defined as eGFR <60 mL/min/1.73 m2) will 
be 2-mg QD (see Section 5.5.1).
c
Some of the first patients randomized during Stage 2 may have begun washout during Stage 1. 
Figure JAHO.1.
Illustration of randomization schemes and enrollment during the 
2 stages of the protocol, before and after the Decision Point.
Study Design
The study design includes 5 periods:  a 5-week screening period, a 36-week double-blind, 
placebo-controlled treatment period, a 68-week long-term extension period, a 96-week bridging 
extension, and a posttreatment follow-up period.  The SOA (Section 2) will be the same for 
patients randomized during Stage 1 and Stage 2 except some patients enrolled during Stage 1 
may have an unscheduled visit(s) after the Decision Point (see Section 5.1.6).
Figure JAHO.2 illustrates the study design.  The full visit schedule is outlined in the SOA 
(Section 2).

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Abbreviations:  AA-IGA = Alopecia Areata Investigator Global Assessment; ClinRO = clinician reported outcome; EC = exclusion criterion; eGFR = estimated 
glomerular filtration rate; ET = early termination; IP = investigational product; PBO = placebo; PTFU = posttreatment follow-up; QD = once daily 
administration; RW = randomized withdrawal; SALT = Severity of Alopecia Tool; V = Visit.

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a
Applicable to all patients at time of screening. See EC [9] for treatments that will require washout.
b
The maximal baricitinib dose for patients with renal impairment (defined as eGFR <60 mL/min/1.73 m2) will be 2-mg QD (see Section 5.5.1).
c
At Week 36 patients in the placebo treatment arm who have NOT achieved SALT ≤20 will be rescued and re-randomized in a 1:1 ratio to baricitinib 2-mg or 
baricitinib 4-mg.  All patients in the baricitinib treatment arms will continue in their current treatment arm regardless of treatment response at Week 36.  
Patients in the placebo arm who have achieved a SALT ≤20 will remain on placebo at Week 36. These patients who have experienced spontaneous regrowth 
on the scalp will remain on placebo for the remainder of the trial, even if relapse is observed later during the study.
d
At Week 52, responders, SALT ≤20, who are eligible (i.e., stayed on the same dose of baricitinib from initial randomization at Visit 2) will be randomized in
a 3:1 ratio to either stay on their current dose of baricitinib or transition to placebo (randomized withdrawal).
e
Patients who have been in the baricitinib 4-mg treatment group from Baseline and who have never achieved a SALT ≤20 by Week 52 AND do not have a ≥2 
point improvement in ClinRO measure for eyebrow or eyelash hair loss (nonresponders) at Week 52 will be automatically transitioned to placebo. See
footnote “f” for discontinuation criteria at Week 76.
f
Patients who are nonresponders, SALT >20, at Weeks 52 AND 76 will be automatically discontinued from the study at Week 76, unless they have a ≥2-point
improvement from baseline in ClinRO measure for eyebrow or eyelash hair loss.  See Section 5.1.6 for more details.
g
Responders who experience a loss of treatment benefit after Week 52 (>20-point absolute worsening in SALT score) who were randomized to placebo at 
Week 52 (randomized withdrawal) will be retreated with their baricitinib dose, as randomized at Baseline (Visit 2).  Patients who were randomized to remain 
on baricitinib (randomized withdrawal) will continue to receive the same dose of baricitinib. See Section 5.1.6 for more detail.
h
ET Visit is required for patients that terminate IP early.  Patients who remain in the study for more than 28 days after discontinuation of IP do not need a 
separate follow-up visit (V801).
i
V801 occurs approximately 28 days after the last dose of IP. Patients who have completed Week 200 and will continue on marketed product beyond Week 
200 do not need to complete Period 5.
j
Patients who are nonresponders at Week 52 and who have been in the baricitinib 2-mg treatment group from Baseline will be rescued to baricitinib 4-mg.  
Figure JAHO.2.
Illustration of study design for Clinical Protocol I4V-MC-JAHO.

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5.1.1.
Stage 1 (Includes Phase 2 Portion and Phase 3 Portion 
before Decision Point)
The objective in the Phase 2 portion of JAHO is to identify up to 2 baricitinib doses that will 
continue into Phase 3, or to stop the study early for futility.  
Stage 1:
A maximum of approximately 300 patients are expected to enroll during Stage 1.

The first approximately 100 patients (Phase 2) will be randomized in a 1:1:1:1 ratio to 
placebo, baricitinib 1-mg once daily (QD), baricitinib 2-mg QD, or baricitinib 4-mg QD
(see Figure JAHO.1). Patients will be stratified at randomization by geographic region 
(North America and Japan), and duration of current episode at Baseline (less than 4 years 
versus at least 4 years).

An interim analysis, as described in Section 10.3.7, will be conducted after 100 patients 
who have been randomized and treated (approximately 25 from each dose level) have 
reached Week 12 (Visit 5) or discontinued early, to determine which of the 3 baricitinib 
doses qualify to continue into Phase 3.  

Patients will continue to be enrolled in Stage 1 until the Decision Point is reached:
approximately up to 200 additional patients will be included in the Phase 3 portion of the 
study and will be randomized in a 2:2:3 ratio to placebo, baricitinib 2-mg QD or
baricitinib 4-mg QD, as it is anticipated that the 1-mg dose will be the dose most likely to 
be dropped after the Decision Point. Patients will be stratified at randomization by 
geographic region (North America, Asia, and Rest of World) and duration of current 
episode at Baseline (less than 4 years versus at least 4 years).
Note:  Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 
who are randomized to baricitinib 4-mg will receive a dose of 2-mg QD. 
Patients enrolled during Stage 1 will undergo the same visits and procedures described below for 
patients enrolled during Stage 2, as shown in Figure JAHO.2; however, some patients enrolled 
during Stage 1 may have up to 2 unscheduled visits after the Decision Point, as described in 
Section 5.1.2.
5.1.2. Decision Point
The Decision Point is the point in time when up to 2 baricitinib doses will be selected to continue 
in Stage 2, or the study will be stopped for futility based on the outcome of the Phase 2
population, Week 12 interim analysis. Based on this interim analysis, the 4-mg and 2-mg doses 
of baricitinib were selected to continue into the Phase 3 portion of Study JAHO.
Patients in the baricitinib treatment arm that is not selected at the Decision Point 
(baricitinib 1-mg) will remain in the study, and they will be transitioned to the highest dose of 
baricitinib remaining in the study (4-mg) at the next study visit following the Decision Point.

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Patients and sites will remain blinded to treatment allocation after the Decision Point and, 
therefore, will not know which patients will be transitioned.  Transition will automatically occur 
at the next visit after Decision Point; this will be referred to as the Transition Visit.  A patient 
should be seen within 8 weeks following the Decision Point being communicated to the sites.  If 
there is not a regularly scheduled visit during this timeframe, patients may be brought in for an 
unscheduled visit.  A patient should be seen within 8 weeks following the Transition Visit to 
perform laboratory tests for safety review.  If there is not a regularly scheduled visit during this 
timeframe, patients may be brought in for an unscheduled visit (see Schedule of Activities 
[Section 2] for detailed requirements).  After the Decision Point, all patients enrolled during 
Stage 1 will follow all protocol procedures for Periods 2, 3, and 4.  
5.1.3. Stage 2 (Remaining Portion of Phase 3 Study after the Decision 
Point)
Approximately 425 additional patients will be enrolled in a 2:2:3 ratio to placebo, baricitinib 
2-mg QD, or baricitinib 4-mg QD, as shown in Figure JAHO.2.  Patients will be stratified at 
randomization by geographic region (North America, Asia, and Rest of World) and duration of 
current episode at Baseline (less than 4 years versus at least 4 years).
5.1.4. Period 1:  Screening (-35 to -3 days)
The duration of the Screening Period is between 3 and 35 days prior to Visit 2 (Week 0).  
Therapies that must be washed out or discontinued before randomization (Visit 2) are listed in 
exclusion criteria [9].  Patients who receive a purified protein derivative (PPD) skin test at 
Visit 1 will return 48 to 72 hours later to read the skin test.  Patients who are eligible for herpes 
zoster vaccine (per local guidelines) and have not previously received the vaccine will be 
encouraged to do so prior to randomization. Vaccination with the live herpes zoster vaccination 
(single injection) must occur at least 28 days (4 weeks) prior to randomization.  Vaccination with 
the non-live herpes zoster vaccine requires 2 injections administered at least 8 weeks apart. It is 
recommended that patients who have initiated vaccination with the non-live herpes zoster 
vaccine receive the second dose at least 4 weeks prior to randomization. For both vaccines, 
completion of the vaccination may require rescreening the patients to comply with the maximum 
allowed duration of the screening period.  In addition, investigators should review the 
vaccination status of their patients and follow the local guidelines for vaccination of those 
≥18 years of age with non-live vaccines intended to prevent infectious disease prior to entering 
patients into the study.  Patients who meet all of the inclusion criteria (Section 6.1) and none of 
the exclusion criteria (Section 6.2) will continue to Visit 2.
5.1.5. Period 2:  Double-Blind Treatment Period (Weeks 0 – 36)
At Visit 2 (Week 0, Baseline), study eligibility for each patient will be reviewed on the basis of 
all inclusion (Section 6.1) and exclusion (Section 6.2) criteria and laboratory test results.  
Patients who meet all eligibility criteria will proceed to randomization and begin the 36-week 
double-blind, placebo-controlled treatment period (Study Period 2). 

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At Visit 2, after laboratory samples are collected and all assessments are completed, patients will 
take the first dose of IP in the clinic. Pharmacokinetic (PK) samples will be drawn 15 minutes 
and 1 hour after the dose. See Section 9.5 for the timing of PK sampling at Visits 3, 4, 5, and 6 
or the early termination (ET) (if ET occurs prior to Visit 6).
Please refer to Section 5.1.1 for enrollment and randomization details of Stage 1 (before 
Decision Point), Section 5.1.2 for details of the Decision Point, and Section 5.1.3 for enrollment 
and randomization details of Stage 2. 
During Study Period 2 (double-blind treatment), medications listed in Section 7.7.2 will be 
prohibited.  
At Baseline (Visit 2), photographs of the scalp (4 planes), 1 photograph (frontal view) of the face 
and scalp, and photographs of the eyebrows/eyelashes will be obtained from all patients; 
photographs of nails will be obtained only from patients who have nail involvement (clinician 
reported outcome [ClinRO™Measure for Nail Appearance] ≥1) at Baseline. At Week 12 
(Visit 5), photographs of the scalp (4 planes) and 1 photograph (frontal view) of the face and 
scalp will be obtained from all patients and photographs of eyelashes/eyebrows and/or nails will 
be captured only from patients who have AA involvement (ClinRO ≥1) of those areas at 
Baseline, as assessed by investigator (see SOA [Section 2] and Section 9.1.4).  Missed 
photographs will not be considered a protocol violation.  Detailed requirements for photography 
are located in the Photography Manual. 
The primary efficacy endpoint will be at Week 36 (Visit 8).  If a patient discontinues IP prior to 
Week 36 (Visit 8), the patient is encouraged to remain in the study and follow the regular visit 
schedule to provide the primary efficacy and safety data through Week 36 (Visit 8).
5.1.6. Period 3:  Long-Term Extension
All patients who have completed Study Period 2 (Week 36) will enter the long-term extension 
period (up to 68-weeks of additional treatment [Study Period 3]). Patients will continue on their 
current treatment assignment unless predefined criteria are met for rescue.
Photographs will be obtained at Weeks 36 and 52, as described in the SOA (Section 2) and 
Section 9.1.4; however, missed photographs will not be considered a protocol violation.  
Photographs will be obtained at ET for patients who discontinue prior to Week 52.
During Study Period 3 (long-term extension), medications listed in Section 7.7.2 will be 
prohibited.  
At Week 36 
The predicted enrollment rate for Study JAHO suggests that some of the patients enrolled during 
Stage 1 may reach Week 36 before the Decision Point is achieved.  See Section 5.1.2 for 
additional details on transitioning patients after the Decision Point:

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
Patients in the placebo treatment arm who have not achieved SALT ≤20 at Week 36, 
AND who reach the Week 36 Visit: 
o
prior to the Decision Point, will be rescued to baricitinib and randomized in a 
1:1 ratio to baricitinib 2-mg or baricitinib 4-mg.
o
after the Decision Point, will be rescued to baricitinib and randomized in a 
1:1 ratio to baricitinib 2-mg or baricitinib 4-mg. 

Patients in the placebo arm who have achieved a SALT ≤20 will remain on placebo at 
Week 36.  These patients who have experienced spontaneous regrowth will remain on 
placebo for the remainder of the trial, even if relapse is observed later during the study.

All patients in the baricitinib treatment arms will continue in their current treatment 
group, regardless of their treatment response at Week 36 (refer to Week 52 and Week 76
sections below for additional rescue information and discontinuation criteria).
At Week 52
Responders:  SALT ≤20 

Patients in baricitinib treatment arms who achieve a SALT ≤20 at Week 52 (responders) 
are eligible for randomized withdrawal, provided that they have stayed on the same dose 
of baricitinib from initial randomization (Visit 2).  

Responders who have had a change in dose after the Decision Point, or patients who were 
rescued to baricitinib at Week 36, will not be eligible for randomized withdrawal and will 
remain in their same treatment group.  

Eligible patients will be automatically randomized in a blinded manner by the IWRS in a 
3:1 ratio to either stay on their current dose of baricitinib or transition to placebo 
(randomized withdrawal).  

Any patients in the placebo treatment arm at Week 52 who have achieved a SALT ≤20 
will remain on placebo.

Responders who experience a loss of treatment benefit after Week 52 (defined as 
>20-point absolute worsening in total SALT score), and who:
o
were randomized to placebo at Week 52 (randomized withdrawal), will be 
automatically retreated with their baricitinib dose, as randomized at Baseline 
(Visit 2).
o
remained on baricitinib at Week 52 (randomized withdrawal), will continue to 
receive the same dose of baricitinib.
o
were randomized to placebo at Baseline (Visit 2), will remain on placebo. 
Note:  An unscheduled visit may be used after Week 52 to assess the patient who reports a loss 
of treatment response (see Schedule of Activities [Section 2] for detailed requirements).  
Nonresponders:  SALT >20

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
Patients who have been in the baricitinib 4-mg treatment group from Baseline AND have 
never achieved a SALT ≤20 by Week 52 AND do not have a ≥2-point improvement from 
Baseline in ClinRO measure for eyebrow or eyelash hair loss at Week 52 will be 
automatically transitioned to placebo.

Patients who have been in the baricitinib 4-mg treatment group and have achieved a 
SALT ≤20 before Week 52 and have lost response, will remain on baricitinib 4-mg dose.

Those who have been in the baricitinib 2-mg treatment group from Baseline will be 
rescued to baricitinib 4-mg.

Those who were transitioned to baricitinib 4-mg after the Decision Point, or were rescued 
to baricitinib at Week 36, will continue in their current treatment arm at Week 52.
Week 76

Patients who are nonresponders (SALT >20) at Weeks 52 AND 76 will be automatically 
discontinued from the study at Week 76, unless they have a ≥2-point improvement from 
baseline in ClinRO measure for eyebrow or eyelash hair loss.
5.1.7. Period 4:  Bridging Extension
Patients who have completed Week 104 and have not met criteria for permanent discontinuation 
will have the possibility to remain in the trial for up to 96 additional weeks (up to Week 200).
During Period 4, patients will continue to receive the same treatment they received during Period 
3.
Responders who had been randomized to placebo at Week 52 (randomized withdrawal) and have 
remained on placebo, will have the possibility to be retreated with their baricitinib dose as 
randomized at Baseline (Visit 2) if they experience a loss of benefit (defined as >20-point 
absolute worsening in total SALT score).
5.1.8. Period 5:  Posttreatment Follow-Up
Patients who complete the study through Visit 24 (Week 200), will have a posttreatment 
follow-up visit (Visit 801) approximately 28 days after the last dose of IP.  Patients who have 
completed Week 200 and who will continue on marketed product beyond Week 200 do not need 
to complete Period 5 (Visit 801).
Patients who have received at least 1 dose of IP and discontinue early from the study must have 
an ET, and return for the posttreatment safety follow-up visit (Visit 801) approximately 28 days 
after the last dose of IP.
Patients who have discontinued IP product but remain in the study for more than 28 days without 
IP will have an ET if they choose to discontinue early; however, a separate follow-up visit 
(V801) is not required.

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5.2.
Number of Participants
Planned enrollment is approximately 100 patients in Phase 2 and approximately 625 patients in 
Phase 3.  A maximum of approximately 300 patients will be enrolled during Stage 1 (approximately
100 patients in Phase 2, and 200 patients in Phase 3).  The remaining approximately 425 patients 
for Phase 3 will be enrolled during Stage 2. Approximately 1035 patients in total will be 
screened to meet the planned total enrollment of 725 patients. 
5.3.
End of Study Definition
End of study is the date of the last visit or last scheduled procedure shown in the SOA (Section 2)
for the last patient.
5.4.
Scientific Rationale for Study Design
Available data strongly suggest that AA results from an immune-mediated perturbation of hair 
follicle biology due to pro-inflammatory mediators, such as IFNγ and other cytokines utilizing 
JAK-STAT signaling.  Therefore, there is strong scientific and immunological rationale for 
studying the ability of baricitinib to restore hair follicle growth in AA patients. Because the IFNγ
receptor engages both JAK1 and JAK2, the dual mechanism of action for baricitinib that inhibits 
both JAK1 and JAK2 is ideally suited for drug selection for patients with AA.  The results of the 
interim analysis of the Phase 2 portion of this study confirm the potential of baricitinib to restore 
hair growth in patients suffering from AA.  By employing a seamless Phase 2/3 study design, 
rapid progress can be made to fill the current therapeutic void and unmet need.
A washout of systemic and topical treatments for AA is incorporated before randomization to 
minimize confounding effects of prior treatment.  Durations of required washouts take into 
consideration that several weeks may be necessary before observing regrowth of hair in treated 
AA patients.  
This trial will enroll patients with severe AA (defined as a SALT score of 50% to 95%) and very 
severe AA (defined as a SALT score of 95% to 100%), as patients with more limited, scattered 
patches are often treated with topical corticosteroids or intralesional corticosteroid injections 
(eg, triamcinolone) and topical minoxidil.  There is no approved treatment for the management 
of AA; therefore, this trial will evaluate the efficacy and safety of 2 doses of baricitinib in 
Phase 3 (baricitinib 2-mg and 4-mg QD) versus placebo.
Eligible patients have at least 6 months of disease with no spontaneous improvement during this 
period, as spontaneous remissions of AA can be observed during the first months after onset. 
Hence, minimal chances of spontaneous hair regrowth confounding the ability of baricitinib to 
facilitate hair follicle regrowth were designed into this study.
The primary endpoint is the proportion of patients reaching a SALT ≤20 (i.e., ≤20% of scalp 
involvement) and will be evaluated after 36 weeks of treatment.  Experience with other drugs has 
shown that it can take several months for patients with AA under treatment to grow new hair.  It 
is expected that several weeks of treatment will be necessary to allow hair follicles to cycle back 

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to anagen phase after control of the inflammatory response leading to hair regrowth, and that it 
could take up to 9 months to observe maximum efficacy.  
Alopecia areata is a chronic and relapsing condition, and some patients may require continuous 
treatment.  Patients with SALT ≤20 at Week 52 and who have received the same dose of 
baricitinib over 52 weeks, will be randomized to either stay on treatment or transition to placebo 
(in a 3:1 ratio) to observe the consequence of treatment interruption.  These patients will be 
retreated with their initial baricitinib dose if they present with a relapse (loss of >20 points in 
total SALT score).
Period 4 will provide patients who have completed the Week 104 visit and have not met criteria 
for permanent discontinuation, the possibility to remain in the trial for up to 96 additional weeks 
(up to Week 200).  This will allow for additional long-term efficacy and safety information to be 
collected, and provide patients the opportunity to continue study treatment until the anticipated 
approval of baricitinib in this indication.
5.4.1. Rationale for Use of an Adaptive Operationally Seamless 
Design
Alopecia areata likely results from loss of the immune privilege of the hair follicle, resulting in 
its destruction.  Several months of treatment may be necessary to observe maximum efficacy 
with treatment.  Therefore, a classical sequential approach of a Phase 2 dose-ranging study 
followed by two Phase 3 studies would delay the evaluation of the benefit/risk for baricitinib in 
severe or very severe AA, for which there is currently no approved drug available.  
Improvements in trial designs that yield more information earlier about the drug may reduce late-
stage attrition rates, improve selection of the “right” doses for Phase 3, or terminate development 
of ineffective or unsafe therapies earlier.  Novel clinical trial designs, such as adaptive designs, 
offer opportunities to address these issues.  The Pharmaceutical Research and Manufacturers of 
America Working Group has expressed that adaptive designs can be utilized beneficially in dose-
finding and operationally seamless Phase 2/3 trial designs (Gallo et al. 2006).An adaptive design 
refers to a clinical trial design that uses accumulating data to decide how to modify aspects of the 
study as it continues, without undermining the validity and integrity of the trial (Gallo et al. 
2006).  The goal of adaptation is to learn from the accumulating data and to apply what is 
learned as quickly as possible.  In order to maintain the validity and integrity of the trial, the 
adaptations must be pre-specified.
Study JAHO, an adaptive, operationally seamless Phase 2/3 trial, is one of two pivotal trials 
planned for the clinical development of baricitinib in adult patients with severe or very severe
AA.  A number of factors governed the decision to utilize this design.  Based on available 
preclinical and clinical data, the adaptive design feature is believed to afford more efficient use 
of patient safety and efficacy data to characterize the baricitinib dose-response relationship and 
to improve data-driven decisions.  The operationally seamless component will allow trial 
objectives that are normally achieved through separate trials in Phase 2 and 3 to be addressed in 
a single trial.  Specifically, the adaptive dose-finding design should lead to a dose selection
decision of the type normally associated with Phase 2.  The Phase 3 confirmatory efficacy 

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objective will be achieved by comparing the safety and efficacy of the selected baricitinib doses 
to placebo.  This operationally seamless design will also provide longer-term safety data earlier 
in the clinical development program.
If Stage 1 of Study JAHO leads to a decision on baricitinib dose selection, the trial will proceed 
into the second stage by seamlessly shifting to a fixed-patient allocation scheme, including 
2 active arms versus placebo. Patients assigned to the selected baricitinib doses and placebo will 
remain in the same treatment group.  Patients initially assigned to the dose that is discontinued 
will be transitioned to the highest selected dose.  The study schedule will be the same for both 
stages.  Data from patients enrolled before and after adaptation in the baricitinib doses selected 
and placebo, excluding those enrolled in the Phase 2 portion, will be used for statistical inference 
in the primary analysis.  Therefore, the operationally seamless design will not make inference 
complicated due to the possibility of type I error inflation which cannot be quantified in a setting 
of dose modification. 
5.5.
Justification for Dose
The doses proposed for Study JAHO are baricitinib 1-mg, 2-mg, and 4-mg QD.  These doses 
were chosen primarily based on the recently completed Phase 2 AD study, JAHG, and are 
additionally supported by PK, safety, and efficacy data for baricitinib in Phase 2 and Phase 3 RA 
studies and a Phase 2 psoriasis study.
In a Phase 2 study conducted in patients with moderate-to-severe atopic dermatitis (Study I4V-
MC-JAHG [JAHG]), both the 2-mg and 4-mg doses showed benefit on the primary and major 
secondary endpoints, 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 
more stringent endpoints, compared to the 2-mg dose, particularly in the subgroup of patients 
with more severe disease at Baseline.  The 4-mg dose resulted in statistically significant 
improvement in the more stringent 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, 2-mg and 4-mg doses 
showed similar efficacy, compared to placebo.  Thus, based on available data, 3 doses will be 
included in the Phase 2 part of this study, including a 1-mg dose, to cover the range of exposures 
where clinical responses could be anticipated.  The results of the Week 12 interim analysis of the 
Phase 2 part of Study JAHO showed that for both SALT30 (at least 30% improvement from 
Baseline in SALT score) at Week 12 and SALT50 (at least 50% improvement from Baseline in 
SALT score) at Week 16, the 2-mg and 4-mg baricitinib doses demonstrated numerical 
superiority over placebo and the 1-mg dose. For SALT50 at Week 16, the difference between the 
4-mg dose and placebo was statistically significant (p=.036). In the patients with greater disease 
severity (AA-IGA = 4), the 4-mg dose seemed to provide a more distinct response when 
compared to the 2-mg dose and the 2-mg dose a more distinct response when compared to the 1-
mg dose and placebo, although this observation will need to be confirmed on larger sample sizes.
These results were confirmed by the second interim analysis of Phase 2 portion of Study JAHO 

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conducted after 36 weeks of treatment. There were no SAEs during the period of treatment and 
no new safety findings. 
The pharmacokinetic data from sparse sampling suggest that the systemic exposure in AA 
patients increases in a dose-dependent manner (approximately dose proportional) across the 
range from 1-mg to 4-mg. Moreover, the population level exposure of baricitinib for AA 
patients is similar to that of atopic dermatitis patients and lower than that of rheumatoid arthritis 
patients. 
Altogether, these data support further evaluation of baricitinib 2-mg QD and 4-mg QD regimen 
in the Phase 3 program of baricitinib in Alopecia Areata, which includes the Phase 3 part of 
Study JAHO and Study JAIR.
5.5.1. Rationale for Dose Adjustment for Renal Impairment 
Baricitinib exposure increases with decreased renal function.  Based on PK simulations of 
baricitinib exposures for the mild and moderate categories of renal function (stratified as eGFR 
60 to <90 mL/min/1.73 m2 and eGFR 30 to <60 mL/min/1.73 m2, respectively), dose adjustment is 
not required for patients with eGFR ≥60 mL/min/1.73 m2.  Patients with eGFR <60 mL/min/1.73 m2
who are randomized to the 4-mg dose will receive a dose of 2-mg QD, which will ensure that 
exposures do not exceed those of the 4-mg QD dose in patients with eGFR ≥60 mL/min/1.73 m2.  
For patients randomized to the 2-mg dose or 1-mg dose, there will be no dose adjustment based 
on renal function.  The dose adjustment for renal impairment will be managed by IWRS to 
ensure maintenance of the treatment blind.  This study will not enroll patients with screening 
eGFR <40 mL/min/1.73 m2.  See Section 8.1.1 for eGFR thresholds that trigger interruption of 
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
Prospective approval of protocol deviations to recruitment and enrollment criteria (also known as 
protocol waiver or exemption) is not permitted.
Study investigator(s) will review patient history and screening test results at Visit 1 and Visit 2 to 
determine if the patient meets all inclusion criteria and none of the exclusion criteria to qualify 
for randomization in the study.  All screening activities must be completed and reviewed before 
the patient is randomized.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria at 
screening:
Informed Consent
[1]
Are at least 18 years and ≤60 years for males (≤70 years of age for females) at the 
time of informed consent.
Note:  Use local requirements to provide consent if the age of adulthood is defined as 
>18 years.  Different upper age limits have been included for male and female 
patients, based on difference in the prevalence of concomitant androgenetic alopecia.  
[2]
Are able to read, understand, and give documented (electronic or paper signature) 
informed consent.
Type of Patient and Disease Characteristics
[3]
Have severe or very severe AA, as determined by all of the following:
a.
Current AA episode of more than 6 months’ duration and hair loss encompassing 
≥50% of the scalp, as measured by SALT (AA-IGA of 3 or 4) at Visit 1 AND Visit 
2.
b. No spontaneous improvement (i.e., no more than 10 point spontaneous reduction in 
SALT) over the past 6 months.
c.
Current episode of severe or very severe AA of less than 8 years. 
Note: patients who have severe or very severe AA for ≥8 years may be enrolled if 
episodes of regrowth, spontaneous or under treatment, have been observed on the 
affected areas of the scalp over the past 8 years.
[4]
Agree not to use any AA treatments during the study, including, but not limited to:
a.
systemic therapies (eg, methotrexate, cyclosporine, corticosteroids, JAK inhibitors, 
apremilast, dimethyl fumarate derivatives, hydroxychloroquine, mycophenolate-
mofetil, IFNγ, azathioprine) and biologics (eg, monoclonal antibodies) 
b. intralesional corticosteroid injections

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c.
topical therapies, including irritants and immunotherapies (eg, 
diphenylcyclopropenone) 
d. Phototherapy, including lasers
e.
Platelet-rich plasma injection
f.
HMG CoA reductase inhibitors or “Statins” (eg, simvastatin, simvastatin + 
ezetimibe) for treatment of AA.
g. Cryotherapy
Note:  Treatment with bimatoprost ophthalmic solution for eyelashes may be continued if the 
patient has been on a stable dose for 8 weeks prior to randomization.  Treatment with finasteride 
(or other 5 alpha reductase inhibitors) or oral or topical minoxidil may be continued if the patient 
has been on a stable dose for 12 months and is anticipated to continue on a stable dose up until 
Week 36. 
[5]
Are male or nonpregnant, nonbreastfeeding female patients
a.
Male patients will either remain abstinent (if this is their preferred and usual 
lifestyle) or agree to use 2 forms of birth control (1 must be highly effective, see 
below) while engaging in sexual intercourse with female partners of childbearing 
potential and agree to not father a child while enrolled in the study and for at least 
4 weeks following the last dose of IP.  Men who are in exclusively same-sex 
relationships (when it is their preferred and usual lifestyle) are not required to use 
contraception.
b. Female patients of child-bearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as 
part of their preferred and usual lifestyle) must agree to either remain abstinent or 
stay in a same-sex relationship without sexual relationships with males.  Periodic 
abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), 
declaration of abstinence just for the duration of a trial, and vaginal withdrawal are 
not acceptable methods of contraception.
Otherwise, female patients of childbearing potential must agree to use 2 forms of 
birth control, when engaging in sexual intercourse with male partners 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 to be used with their male partners, and 1 must be highly effective):

Highly effective birth control methods:  oral, injectable, or implanted hormonal 
contraceptives (combined estrogen/progesterone or progesterone only, 
associated with inhibition of ovulation); intrauterine device or intrauterine 
system (eg, progestin-releasing coil); or vasectomized male (with appropriate 
post-vasectomy documentation of the absence of sperm in the ejaculate). 

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
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 that do not inhibit ovulation. 
Note:  When local guidelines concerning highly effective or effective methods 
of birth control differ from the above, the local guidelines must be followed.
c.
Females of nonchildbearing potential are not required to use birth control.  They 
are defined as:  

women ≥60 years of age or women who are congenitally sterile, or

women ≥40 and <60 years of age who have had a cessation of menses for 
≥12 months and a follicle-stimulating hormone (FSH) test confirming 
nonchildbearing potential (≥40 mIU/mL or ≥40 IU/L), or women who are 
surgically sterile (i.e., have had a hysterectomy or bilateral oophorectomy or 
tubal ligation).
6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
Medical Conditions Related to AA
[6]
primarily “diffuse” type of AA (characterized by diffuse hair shedding)
[7]
are currently experiencing other forms of alopecia, including but not limited to:  
androgenetic alopecia (male pattern Grade IV or greater using Hamilton-Norwood 
classification, or female pattern), trichotillomania, telogen effluvium, chemotherapy-
induced hair loss or any other concomitant conditions (eg, tinea capitis, psoriasis, 
lupus erythematosus, or secondary syphilis) that would interfere with evaluations of 
the effect of study medication on AA.
[8]
Patients who, in the opinion of the investigator, are currently experiencing or have a 
history of unstable concomitant disease that requires frequent hospitalizations and/or 
frequent use of systemic immunosuppressants that may interfere with participation in 
the study.
[9]
Have been treated with the following therapies:
a.
Corticosteroids
i. Topical corticosteroids applied to the scalp or eyebrows within 1 week prior to 
randomization.
ii. Systemic corticosteroids within 8 weeks prior to randomization.
iii. Intralesional corticosteroid injections for treatment of AA within 8 weeks 
prior to randomization.

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iv. Have had an intraarticular corticosteroid injection within 8 weeks prior to 
randomization.
Note:  Intranasal, ophthalmic, or inhaled steroid use is allowed during screening and 
throughout the study.
b.
JAK inhibitors
i. Topical JAK inhibitor applied to the scalp (eg, tofacitinib, ruxolitinib) within 
4 weeks prior to randomization.
ii. Oral JAK inhibitor within 8 weeks prior to randomization.  
iii. Previously treated with an oral JAK inhibitor (eg, tofacitinib, ruxolitinib) and 
had an inadequate response (for example, absence of significant terminal hair 
growth after at least 12 weeks of treatment). 
c.
Other topical therapies (eg, anthralin, diphenylcyclopropenone, or other topical 
immunotherapies) for the treatment of AA within 4 weeks prior to randomization.
d.
Monoclonal antibody (eg, ustekinumab, secukinumab, adalimumab, dupilumab) 
less than 5 half-lives prior to randomization.
e.
Probenecid at the time of the randomization (Visit 2) that cannot be discontinued 
for the duration of the study (probenecid may increase baricitinib exposures).
f.
Platelet-rich plasma within 8 weeks prior to randomization.
g.
Phototherapy (UV therapy and laser on scalp lesions) within 4 weeks prior to 
randomization.
h.
HMG CoA reductase inhibitors or “Statins” (e.g., simvastatin, simvastatin + 
ezetimibe) for treatment of AA within 4 weeks prior to randomization.
i.
Cryotherapy for treatment of AA within 4 weeks prior to randomization.
j.
Finasteride (or other 5 alpha reductase inhibitors) or minoxidil (topical or oral) 
within 8 weeks prior to randomization, unless the subject has been on a stable dose 
for at least 12 months AND is anticipated to continue on a stable dose up until 
Week 36.
k. Immunosuppressants (for example, methotrexate, cyclosporine, dimethyl fumarate 
derivatives, mycophenolate-mofetil, IFNγ, azathioprine) within 8 weeks of 
randomization.
l.
Apremilast or hydroxychloroquine within 4 weeks prior to randomization.
Medical Conditions in General
[10] Are largely or wholly incapacitated, permitting little or no self-care, such as being 
bedridden.
[11] Have uncontrolled arterial hypertension characterized by a repeated systolic blood 
pressure >160 mm Hg or diastolic blood pressure >100 mm Hg in a seated position.

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[12] Have had any major surgery within 8 weeks prior to screening or will require major 
surgery during the study that, in the opinion of the investigator (in consultation with 
Lilly or its designee), would pose an unacceptable risk to the patient if participating in 
the trial.
[13] Are immunocompromised and, in the opinion of the investigator, at an unacceptable 
risk for participating in the study.
[14] Have experienced any of the following within 12 weeks of screening:  myocardial 
infarction, unstable ischemic heart disease, stroke, or New York Heart Association 
Stage III/IV heart failure.
[15] Have a history of VTE, or are considered at high risk for VTE, as deemed by the 
investigator, or have 2 or more of the following risk factors for VTE:
a) Aged >65 years
b) BMI >35 kg/m2
c) Oral contraceptive use and current smoker status
[16] Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, 
endocrine, hematological, neurological, or neuropsychiatric disorders or any other 
serious and/or unstable illness that, in the opinion of the investigator, could constitute 
an unacceptable risk when taking IP or interfere with the interpretation of data.
[17] Have a history of lymphoproliferative disease; or have signs or symptoms suggestive 
of possible lymphoproliferative disease, including lymphadenopathy or 
splenomegaly; or have active primary or recurrent malignant disease; or have been in 
remission from clinically significant malignancy for <5 years.
a.
Patients with cervical carcinoma in situ that has been successfully treated with no 
evidence of recurrence or metastatic disease for at least 3 years may participate in 
the study.
b. Patients with basal cell or squamous cell skin cancers that have been successfully 
treated with no evidence of recurrence for at least 3 years may participate in the 
study.
[18] Have a current or recent and/or serious viral, bacterial, fungal, or parasitic infection, 
including but not limited to the following:
a.
Symptomatic herpes zoster infection within 12 weeks prior to screening.
b. A history of disseminated/complicated herpes zoster (eg, multidermatomal 
involvement, ophthalmic zoster, central nervous system involvement, or 
post-herpetic neuralgia).
c.
Symptomatic herpes simplex at the time of randomization.
d. Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus 
(HCV), or human immunodeficiency virus (HIV).

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e.
Household contact with a person with active tuberculosis (TB) and did not receive 
appropriate and documented prophylaxis for TB.
f.
Evidence of active TB or have previously had evidence of active TB and did not 
receive appropriate and documented treatment.
g. Clinically serious infection, or received intravenous (IV) antibiotics for an 
infection, within 4 weeks prior to randomization.
h. Any other active or recent infection within 4 weeks of randomization that, in the 
opinion of the investigator, would pose an unacceptable risk to the patient if 
participating in the study.
Note:  A recent viral upper respiratory tract infection or uncomplicated urinary tract 
infection should not be considered clinically serious.
[19] A history of eczema herpeticum within 12 months prior to screening.
[20] A history of 2 or more episodes of eczema herpeticum in the past.
[21] Have any serious concomitant illness that is anticipated to require the use of systemic 
corticosteroids or otherwise interfere with study participation or require active 
frequent monitoring (eg, atopic dermatitis, unstable chronic asthma).
[22] Have been exposed to a live vaccine within 12 weeks prior to planned randomization 
or are expected to need/receive a live vaccine during the course of the study (with the 
exception of herpes zoster vaccination).
Note:  Patients eligible for herpes zoster vaccine, who have not received it prior to 
screening will be encouraged (per local guidelines) to do so prior to randomization; 
vaccination with the live herpes zoster vaccine can occur during the screening period 
but must take place >4 weeks prior to randomization and start of IP.  Vaccination 
with the non-live herpes zoster vaccine requires at least 2 injections administered 
8 weeks apart. It is recommended that patients who have initiated vaccination with 
the non-live herpes zoster vaccine receive the second dose at least 4 weeks prior to 
randomization.  For both vaccines, completion of the vaccination may require 
rescreening the patients to comply with the maximum allowed duration of the 
screening period. Patients will be excluded if they were exposed to herpes zoster 
vaccination within 4 weeks of planned randomization.
[23] Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug abuse 
within the 2 years prior to screening.
[24] Presence of significant uncontrolled neuropsychiatric disorder, are clinically judged 
by the investigator to be at risk for suicide, or have a “yes” answer to any of the 
following:
a.
Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific 
Plan) on the “Suicidal Ideation” portion of the Columbia Suicide Severity Rating 
Scale (C-SSRS); or

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b. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the 
“Suicidal Ideation” portion of the C-SSRS; or 
c.
Any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted 
attempt, preparatory act or behavior) on the “Suicidal Behavior” portion of the 
C-SSRS;
and the ideation or behavior occurred within 2 months of Visit 1.
Note:  A patient does not necessarily have to be excluded if they have self-injurious 
behavior that would be classified as nonsuicidal self-injurious behavior.  If this 
situation arises, the patient should be referred to a psychiatrist or appropriately trained 
professional, as indicated.
[25] Have donated more than a single unit of blood within 4 weeks prior to screening or 
intend to donate blood during the course of the study.
Diagnostic Assessments
[26] Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the 
investigator, are clinically significant and indicate an unacceptable risk for the 
patient’s participation in the study.
[27] Have evidence of active TB or latent TB
a.
Have evidence of active TB, defined in this study as the following:
i.
Documented by a positive PPD test (≥5 mm of induration between 
approximately 48 and 72 hours after application, regardless of vaccination 
history), medical history, clinical features, and abnormal chest x-ray at 
screening.
ii.
The QuantiFERON®-TB Gold test or T SPOT.®TB test (as available and if 
compliant with local TB guidelines) may be used instead of the PPD test.  
Patients are excluded from the study if the test is not negative and there is 
clinical evidence of active TB.
Exception:  Patients with a history of active TB who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was 
completed, and have a screening chest x-ray with no evidence of active TB may be 
enrolled if other entry criteria are met.  Such patients would not be required to 
undergo the protocol specific TB testing for PPD, QuantiFERON-TB Gold test, or 
T SPOT.TB test but must have a chest x-ray at screening.
b. Have evidence of untreated/inadequately or inappropriately treated latent TB, 
defined in this study as the following:
i.
Documented to have a positive PPD test (≥5 mm of induration between 
approximately 48 and 72 hours after application, regardless of vaccination 
history), no clinical features consistent with active TB, and a chest x-ray with 
no evidence of active TB at screening; or 

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ii.
PPD test is positive and the patient has no medical history or chest x-ray 
findings consistent with active TB, the patient may have a QuantiFERON-TB 
Gold test or T SPOT.TB test (as available and if compliant with local TB 
guidelines).  If the test results are not negative, the patient will be considered 
to have latent TB (for purposes of this study); or
iii.
QuantiFERON-TB Gold test or T SPOT.TB test (as available and if compliant 
with local TB guidelines) may be used instead of the PPD test.  If the test 
results are positive, the patient will be considered to have latent TB.  If the test 
is indeterminate, the test may be repeated once within approximately 2 weeks 
of the initial value.  If the repeat test results are again not negative, the patient
will be considered to have latent TB (for purposes of this study).
Exception:  Patients who have evidence of latent TB may be enrolled if they complete 
at least 4 weeks of appropriate treatment prior to randomization and agree to 
complete the remainder of treatment while in the trial.
Exception:  Patients with a history of latent TB who have documented evidence of 
appropriate treatment, have no history of re-exposure since their treatment was 
completed, and have a screening chest x-ray with no evidence of active TB may be 
enrolled if other entry criteria are met.  Such patients would not be required to 
undergo the protocol-specific TB testing for PPD, QuantiFERON-TB Gold test, or T 
SPOT.TB test but must have a chest x-ray at screening.
[28] Have a positive test for HBV infection defined as:
a.
Positive for hepatitis B surface antigen (HBsAg), or
b.
Positive for hepatitis B core antibody (HBcAb) and positive HBV 
deoxyribonucleic acid (DNA).
Note:  Patients who are HBcAb-positive and HBV DNA-negative may be 
enrolled in the study.  Patients who meet these criteria at screening will be 
identified by the central laboratory and will need to be monitored during the 
study.
[29] Have HCV infection (positive for anti-hepatitis C antibody with confirmed presence 
of HCV ribonucleic acid (RNA)
Note:  Patients who have documented anti HCV treatment for a past HCV 
infection AND are HCV RNA negative may be enrolled in the study.
[30] Have evidence of HIV infection and/or positive HIV antibodies.
[31] Have screening laboratory test values, including thyroid-stimulating hormone (TSH), 
outside the reference range for the population or investigative site that, in the opinion 
of the investigator, pose an unacceptable risk for the patient’s participation in the 
study.

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Note:  Patients who are receiving thyroxine as replacement therapy may 
participate in the study, provided stable therapy has been administered for 
≥12 weeks and TSH is within the laboratory’s reference range.  Patients who are 
receiving stable thyroxine replacement therapy who have TSH marginally outside 
the laboratory’s normal reference range may participate if the treating physician 
has documented that the thyroxine replacement therapy is adequate for the patient.
[32] Have any of the following specific abnormalities on screening laboratory tests:
a.
AST or ALT ≥2 × the upper limit of normal (ULN)
b.
Alkaline phosphatase (ALP) ≥2 × ULN
c.
TBL ≥1.5 × ULN
d.
Hemoglobin <10.0 g/dL (100.0 g/L)
e.
Total white blood cell count <2500 cells/µL(<2.50 × 103/µL or <2.50 GI/L)
f.
Neutropenia (absolute neutrophil count [ANC] <1200 cells/µL) 
(<1.20 × 103/µL or <1.20 GI/L)
g.
Lymphopenia (lymphocyte count <750 cells/µL) (<0.75 × 103/µL or 
<0.75 GI/L)
h.
Thrombocytopenia (platelets <100,000/µL) (<100 × 103/µL or <100 GI/L)
i.
eGFR <40 mL/min/1.73 m2 (Chronic Kidney Disease Epidemiology 
Collaboration equation [CKD-EPI] creatinine 2009 equation).
Note:  For cases with any of the aforementioned laboratory abnormalities 
(Exclusion Criteria [31] and [32]), the tests may be repeated during screening, and 
values resulting from repeat testing may be accepted for enrollment eligibility if 
they meet the eligibility criterion.
Other Exclusion Criteria
[33] Are unable or unwilling to make themselves available for the duration of the study 
and/or are unwilling to follow study restrictions/procedures. 
[34] Are currently enrolled in any other clinical study involving an investigational product 
or any other type of medical research judged not to be scientifically or medically 
compatible with this study.
[35] Have participated within the last 30 days in a clinical study involving an IP.  If the 
previous IP has a long half-life (2 weeks or longer), at least 3 months or 5 half-lives 
(whichever is longer) should have passed.
[36] Have previously been randomized in this study or any other study investigating 
baricitinib.

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[37] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[38] Are Lilly or Incyte employees or their designee.
6.3.
Lifestyle Restrictions
Study participants should be instructed not to donate blood or blood products during the study.  
It is highly recommended that patients remain consistent with hairstyle and hair coloring during 
the study to facilitate scalp hair assessments.  Patients who prefer to shave their scalp must 
refrain from shaving the scalp within 2 weeks prior to a study visit.  For patients who prefer to 
wear a wig, it is recommended that the wig should not be taped at more than 2 places on the 
periphery of the scalp to avoid pulling the hair.
Patients with eyebrows and/or eyelashes extensions, and/or tattoos, are allowed to be enrolled in 
the trial as long as the degree of eyebrows and eyelashes involvement (and regrowth when 
applicable) can be assessed at every visit. Patients with acrylic nails at screening can be enrolled 
and will not be requested to remove them to enter the trial; no nails assessment or photographs of 
the nails will be required for these patients. Patients who do not wear acrylic nails when they 
enter the trial should refrain from using them before Week 36.
6.4.
Screen Failures
Patients who are entered into the study but do not meet the enrollment criteria for participation in 
this study (screen failure) may be rescreened a maximum of 2 times.  The interval between 
screen failure and rescreenings should be at least 4 weeks.  At the time of rescreening, the 
individual must sign a new informed consent form (ICF), repeat all necessary screening 
procedures, and will be assigned a new identification number. 
If a patient undergoes rescreening, radiographic images acquired as part of initial screening and 
within 6 months of randomization may be used.

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7. Treatments
7.1.
Treatments Administered
The Phase 2 portion (included in Stage 1) of this study involves a comparison of placebo, 
baricitinib 1-mg, baricitinib 2-mg, and baricitinib 4-mg. The Phase 3 portion involves a 
comparison of placebo, baricitinib 2-mg, and baricitinib 4-mg administered orally QD.
Table JAHO.3 shows the treatment regimens and the investigational product (IP) supplied.
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 all unused medication is to be destroyed 
by the site, as allowed by local law
Table JAHO.3.
Treatment Regimen
Treatment Regimen
Investigational Product Supplied
Dose
Baricitinib 4-mg QDa
Baricitinib 4-mg tablets
2 tablets per day
Placebo to match 2-mg tablets
Baricitinib 2-mg QD
Baricitinib 2-mg tablets
2 tablets per day
Placebo to match 4-mg tablets
Placebo QD
Placebo to match 4-mg tablets
2 tablets per day
Placebo to match 2-mg tablets
Abbreviation:  QD = once daily.
a
The baricitinib dose for patients randomized to the 4-mg QD treatment group who have renal impairment 
(defined as eGFR <60 mL/min/1.73 m2) will be 2-mg QD.
7.1.1. Packaging and Labelling
The Sponsor (or its designee) will provide the following IPs:

tablets containing 4-mg of baricitinib

tablets containing 2-mg of baricitinib

tablets containing 1-mg of baricitinib (only for Phase 2 Population, before Decision 
Point)

placebo tablets to match baricitinib 4-mg tablets, 2-mg tablets, and 1-mg tablets (1-mg 
matching placebo tablets only for Phase 2 Population, before Decision Point)
Each tablet has a distinctive shape and color, 4-mg versus 2-mg versus 1-mg, and each strength 
tablet has a matching placebo.  

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During Stage 1:

The first approximately 100 patients randomized will require 3 double-blind tablets per 
day and continue this dosing until the Decision Point;  

The remaining approximately 200 patients randomized during Stage 1, will require 
2 double-blind tablets per day.  
During Stage 2

After the Decision Point, patients who required 3 double-blind tablets per day during 
Stage 1 will be switched to 2 double-blind tablets per day;  

Patients randomized during Stage 2 will require 2 double-blind tablets per day.  
Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.2.
Method of Treatment Assignment
Different randomization schemes will be used at Visit 2:  two during Stage 1 and one during 
Stage 2.  In Stage 1, the first approximately 100 patients who meet all criteria for enrollment will 
be randomized in a 1:1:1:1 ratio to receive placebo QD, baricitinib 1-mg QD, baricitinib 2-mg 
QD, or baricitinib 4-mg QD double-blind treatment at Visit 2 (Week 0).  Up to a maximum of 
approximately 200 additional patients are anticipated to be randomized during Stage 1, prior to 
the Decision Point, in a 2:2:3 ratio to receive placebo QD, baricitinib 2-mg QD or baricitinib 
4-mg QD.  At the Decision Point, baricitinib 4-mg and 2-mg were selected to continue into 
Stage 2. Therefore, after the Decision Point, patients will continue to be randomized in a 2:2:3 
ratio to receive placebo QD, baricitinib 2-mg QD, or baricitinib 4-mg QD. Baseline 
randomization will be stratified by geographic region (North America, Japan [included in the 
Phase 2 portion of the study], and North America, Asia, and Rest of World [included in the 
Phase 3 portion of the study]), and duration of current episode at Baseline (less than 4 years 
versus at least 4 years) for the whole study.  Randomization for the randomized withdrawal will 
not be stratified.  Assignment to treatment groups will be determined by a computer-generated 
random sequence using an IWRS.  The IWRS will be used to assign bottles, each containing 
double-blind IP tablets, to each patient, starting at Visit 2 (Week 0), and at each visit up to and 
including Visit 23 (Week 184).  Site personnel will confirm that they have located the correct 
bottles by entering a confirmation number found on the bottle into the IWRS.
7.2.1. Selection and Timing of Doses
The IP should be taken QD 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. 
Before Decision Point (Stage 1 patients):

Patients will take 3 tablets QD for the first approximately100 patients.

Patients will take 2 tablets QD for the next approximately 200 patients enrolled in 
Stage 1.
After Decision Point:

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
Stage 1 Patients:  All patients after the Decision Point will take 2 tablets QD.

Stage 2 Patients:  All patients will take 2 tablets QD.
7.2.2. Dose Adjustment for Renal Impairment
The rationale of dose adjustment for patients with documented renal impairment (defined as 
screening eGFR ≥40 mL/min/1.73 m2 to <60 mL/min/1.73 m2) is detailed in Section 5.5.1.
The dose adjustment for renal impairment will be managed by IWRS to ensure maintenance of 
the treatment blind.  The eGFR value from the screening visit (Visit 1) will be entered into IWRS 
at Visit 2, and IWRS will assign the treatment doses accordingly.
Patients with documented renal impairment (defined as screening eGFR ≥40 mL/min/1.73 m2 to 
<60 mL/min/1.73 m2), who are randomized to the 4-mg active treatment arm will receive a dose 
of 2-mg QD by the IWRS.  For patients randomized to the 2–mg dose or 1–mg dose, there will 
be no dose adjustment based on renal function.
No dose adjustment will be made for patients with screening eGFR ≥60 mL/min/1.73 m2.  
These patients who are randomized to active treatment will receive their assigned dose, either 
baricitinib 4-mg, 2-mg, or 1-mg, respectively.
During the study, for patients with documented renal impairment when the subsequent eGFR 
falls <30 mL/min/1.73 m2, 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 
patients’ treatment groups.  The Decision Point Committee, an internal committee, will be 
unblinded to the first approximately 100 patients at the Decision Point in Stage 1 but kept
blinded to the remaining patients.  Processes for unblinding the first approximately 100 patients
will be described in the unblinding plan.  
Except in clinical circumstances where unblinding is required, the patients, investigators, Lilly 
study team managing the study, and any other personnel interacting directly with patients or 
investigative sites will remain blinded to baricitinib and placebo assignment until after 
completion of the study.  It is expected that the need for unblinding a patient’s treatment prior to 
completion of the study 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.  The patient’s safety must always be the first consideration in making 
such a determination.  If a patient’s treatment assignment is unblinded, Lilly must be notified

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immediately.  If the investigator decides that unblinding is warranted, it is the responsibility of 
the investigator to promptly document the decision and rationale and notify Lilly as soon as 
possible.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment.  
All unblinding events are recorded and reported by the IWRS.  If an investigator, site personnel 
performing assessments, or patient is unblinded, the patient must be discontinued from the study.  
In cases where there are ethical reasons to have the patient remain in the study, the investigator 
must obtain specific approval from a Lilly clinical research physician for the patient to continue 
in the study.
7.4.
Dosage Modification
As described in Section 5.1.6, some patients may be eligible for rescue to baricitinib at Week 36 
and transition to baricitinib 4-mg or placebo at Week 52.  However, these dose modifications 
will occur automatically through IWRS and, therefore, will not require dose adjustment by the 
sites.
7.5.
Preparation/Handling/Storage/Accountability
All IP (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 study medication will be assessed at each visit during the treatment 
period (Visit 3 through Visit 24) by counting returned tablets.  
A patient will be considered significantly noncompliant if he/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/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, as appropriate, on the importance of taking the IP as 
prescribed.
Patients’ compliance will be further defined in the statistical analysis plan (SAP).
7.7.
Concomitant Therapy
All concomitant medication, whether prescription or over-the-counter, used at Baseline and/or 
during the course of the study, must be recorded on the Concomitant Medication electronic case 
report form (eCRF).  Patients will be instructed to consult the investigator or other appropriate 

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study personnel at the site before taking any new medications or supplements during the study.  
For AA therapies permitted, see Section 7.7.1.
7.7.1. Permitted Medications and Procedures
The following medications are permitted during the study:

Topical corticosteroids except on the scalp, eyebrows, and eyelids.

Topical calcineurin inhibitors except on the scalp, eyebrows and eyelids.

Intranasal, ophthalmic or inhaled steroid use.

A maximum of 2 intra-articular or soft tissue (bursa, tendon, and/or ligament) 
corticosteroid injections are allowed up until the 36-week primary endpoint.  After 
36 weeks, such injections are permitted.

Non-live vaccinations such as seasonal vaccination, non-live herpes zoster (for subjects 
who become eligible during the trial), and/or all emergency vaccinations, such as rabies 
or tetanus vaccinations.

Bimatoprost ophthalmic solution (if on stable dose for 8 weeks prior to randomization).  

Finasteride (or other 5 alpha reductase inhibitors) or oral or topical minoxidil, if on a 
stable dose for 12 months prior to randomization.

HMG CoA reductase inhibitors or “statins” (e.g., simvastatin, simvastatin + ezetimibe) 
for treatment of hypercholesterolemia and the prevention of cardiovascular disease.
Treatment with concomitant therapies for other medical conditions, such as diabetes and 
hypertension is permitted during the study.
7.7.2. Prohibited Medications and Procedures
Any investigational or commercial topical, intra-lesional or systemic therapies (except those listed 
in Section 7.7.1) or phototherapy to treat AA are not allowed during the trial.
In addition, the following medications and procedures are prohibited during the study:
Prohibited Medications and Procedures Requiring Temporary Interruption of 
Investigational Product
The following therapies will not be allowed during the course of the study and, if taken by or 
administered to the patient, temporary interruption of IP is required:

Live vaccines, including Bacillus Calmette-Guérin [BCG] or herpes zoster, 
(see Exclusion Criterion [22]).
o
For BCG vaccination, IP should be temporarily interrupted for 12 weeks.  If BCG 
vaccine is given prior to Week 36, IP should be permanently discontinued.
o
For live herpes zoster vaccination, IP should be temporarily interrupted for 
4 weeks after the injection.  

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
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.

Systemic corticosteroids may be used for the treatment of an AE (eg, worsening of an 
existing condition, such as an 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 IP is required.  

Phototherapy:  Full body UV therapy.
Prohibited Medications Requiring Permanent Discontinuation of Investigational 
Product

Corticosteroids (systemic, intralesional, or topical on the scalp, eyebrows, and/or eyelids) 
for the treatment of AA.  

Topical JAK inhibitors applied to the scalp, eyebrows, and eyelids.

Other oral JAK inhibitors (eg, tofacitinib and ruxolitinib).

Any systemic treatment with an immunosuppressive/immunomodulating substance,
including, but not limited to, cyclosporine, mycophenolate-mofetil, IFNγ, azathioprine, 
methotrexate, dimethyl fumarate derivatives, hydroxychloroquine, or biologics (for 
example, monoclonal antibodies).

Any other AA treatment which has been inadvertently initiated and cannot be
discontinued will lead to permanent discontinuation of IP.
7.8.
Treatment after the End of the Study
7.8.1. Continued Access
Period 4 will provide patients who have completed Week 104 visit and have not met criteria for 
permanent discontinuation, the possibility to remain in the trial for up to 96 additional weeks (up 
to Week 200) and thus provide patients the opportunity to continue study treatment until the 
anticipated approval of baricitinib in this indication.
Study termination may occur in a specific country or region when baricitinib is approved for the 
treatment of AA and becomes reimbursed or commercially available in that country or region, or 
a negative regulatory action or opinion is received in that country or region.
After the conclusion of the study, continued access to baricitinib will not be provided.  Patients 
will be referred to their local treatment centers for AA therapy, as clinically indicated.

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Permanent Discontinuation from Investigational Product 
Investigational product should be permanently discontinued if the patient or the patient’s 
designee requests to discontinue IP.
Discontinuation of the IP for abnormal liver tests should be considered by the investigator when 
a patient meets 1 of the following conditions after consultation with the Lilly-designated medical 
monitor:

ALT or AST >8 × ULN

ALT or AST >5 × ULN for more than 2 weeks

ALT or AST >3 × ULN and TBL >2 × ULN or international normalized ratio (INR) >1.5

ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right 
upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

ALP >3 × ULN

ALP >2.5 × ULN and TBL >2 × ULN

ALP >2.5 × ULN with the appearance of fatigue, nausea, vomiting, right quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (>5%)
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 are observed:

white blood cell count <1000 cells/µL (1.00 × 103/µL or 1.00 GI/L)

ANC <500 cells/µL (0.50 × 103/µL or 0.50 GI/L)

lymphocyte count <200 cells/µL (0.20 × 103/µL or 0.20 GI/L)

hemoglobin <6.5 g/dL (<65.0 g/L)
NOTE:  Temporary interruption rules (see Section 8.1.2) 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 
JAHO.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

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
malignancy (except for successfully treated basal or squamous cell skin carcinoma)

HBV DNA is detected with a value above limit of quantitation (see Section 9.4.8).

certain prohibited medications are taken per Section 7.7.2 (Prohibited 
Medications and Procedures)

development of a VTE 
Note:  Patients who develop a VTE may have additional follow-up and testing 
recommended (see Section 9.4.9 and Appendix 7).
If a patient develops multiple risk factors for a VTE during the conduct of the study, as described 
in Exclusion Criterion [15], the investigator may consider study discontinuation if he/she 
believes the risk outweighs the benefits of continuing therapy.  It is recommended that the 
investigator consult with Lilly (or its designee) before discontinuing therapy for this reason.  
If a patient discontinues IP for any reason, the patient is encouraged to remain in the study 
through Week 36 (Visit 8) and follow the regular visit schedule to provide the primary efficacy 
and safety data.  Patients discontinuing from the IP prematurely for any reason should complete 
AE and other follow-up procedures per Section 2 (Schedule of Activities), Section 9.2 (Adverse 
Events), and Section 9.4 (Safety) of this protocol.
8.1.2. Temporary Interruption of Investigational Product
In some circumstances, it may be necessary to temporarily interrupt treatment as a result of AEs 
or abnormal laboratory values that may have an unclear relationship to IP.  For example, IP
should be temporarily interrupted if the patient experiences a cardiovascular AE considered to be 
related to study treatment, is graded as moderate (Grade 2 according to Common Terminology
Criteria for Adverse Events [CTCAE] Version 3.0), and that does not resolve promptly with
supportive care.  Except in cases of emergency, it is recommended that the investigator consult 
with Lilly (or its designee) before temporarily interrupting therapy for reasons other than those 
defined in Table JAHO.4.  
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table JAHO.4, specific guidance is provided for temporarily interrupting treatment and when 
treatment may be restarted.  Retest frequency and timing of follow-up laboratory tests to monitor 
the abnormal finding are at the discretion of the investigator.  Investigational product that was 
temporarily interrupted because of an AE or abnormal laboratory value not specifically covered 
in Table JAHO.4 may be restarted at the discretion of the investigator.

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Table JAHO.4.
Criteria for Temporary Interruption of Investigational Product
Hold Investigational Product if the Following 
Laboratory Test Results or Clinical Events Occur:
Investigational Product May Be Resumed When:
WBC count <2000 cells/µL
(<2.00 × 103/µL or <2.00 GI/L)
WBC count 2500 cells/µL
(≥2.50 × 103/µL or ≥2.50 GI/L)
ANC <1000 cells/L
(<1.00 × 103/µL or <1.00 GI/L)
ANC ≥1200 cells/µL
(≥1.20 × 103/µL or ≥1.20 GI/L)
Lymphocyte count <500 cells/µL
(<0.50 × 103/µL or <0.50 GI/L)
Lymphocyte count 750 cells/µL
(≥0.75 × 103/µL or ≥0.75 GI/L)
Platelet count <75,000/µL
(<75 × 103/µL or <75 GI/L)
Platelet count 100,000/µL
(≥100 × 103/µL or ≥100 GI/L)
eGFR <40 mL/min/1.73 m2 (from serum creatinine) for 
patients with screening eGFR ≥60 mL/min/1.73 m2
eGFR 50 mL/min/1.73 m2
eGFR <30 mL/min/1.73 m2 (from serum creatinine) for 
patients with screening eGFR ≥40 to <60 mL/min/1.73 m2
eGFR 40 mL/min/1.73 m2
ALT or AST >5 × ULN
ALT and AST return to <2 × 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
VTE ruled out
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.
Although temporary interruption of IP is not a requirement at times of increased potential risk for
VTE (eg, surgery, significant air travel, or other situations involving prolonged immobilization), 
it is recommended that the investigator follow appropriate VTE prophylaxis guidelines to help 
manage the VTE risk under these circumstances. 
For specific guidance on temporary interruption of IP after use of a prohibited medication, please 
refer to Section 7.7.2 (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 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.  

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NOTE:  Prior to resumption of IP, it is recommended that a patient be assessed by a 
psychiatrist or appropriately trained professional to assist in deciding whether the subject 
should remain on IP and, ultimately, continue participation in the study.  A patient does not 
necessarily have to have IP interrupted if he/she has self-injurious behavior that would be 
classified as non-suicidal self-injurious behavior.  
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the Sponsor or investigator identify a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study treatment unless there 
are extenuating circumstances that make it medically necessary for the patient to continue on 
study treatment.  If the investigator and the Sponsor clinical research physician (CRP) agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
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 will be discontinued in the following circumstances:

enrollment in any other clinical study involving an investigational medicinal product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study

participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

investigator decision
o
the investigator decides that the patient should be discontinued from the study
o
if the patient, for any reason, requires treatment with another therapeutic agent for 
AA (not allowed per protocol [Section 7.7.2]) 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 
o
if a patient discontinues IP for any reason, the patient is encouraged to remain in 
the study through Week 36 (Visit 8) and follow the regular visit schedule to 
provide the primary efficacy and safety data  

subject decision
o
the patient or the patient’s designee (eg, parents or legal guardian) requests the 
patient 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 the protocol.

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8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he/she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were, otherwise,
unable to be followed up by the site.

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9.
Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Unless, otherwise, stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Primary Efficacy Assessments
9.1.1.1.
Severity of Alopecia Tool (SALT) Score
The SALT uses a visual aid showing the division of the scalp hair into 4 areas with the top 
constituting 40% of total surface, the posterior/back 24%, right side and left side of scalp 18% 
each.  The percentage of hair loss in each area is determined and is multiplied by the percentage 
of scalp covered by that area.  The total sum of the 4 products of each area will give the SALT 
score, as developed by the National Alopecia Areata Foundation Working Committee 
(Olsen et al. 2004).  Only terminal hair is included in the SALT; vellus hair or any fine downy 
hair is not taken into account in the SALT scoring process (Olsen et al. 1999, 2004).
9.1.2. Secondary Efficacy Assessments
9.1.2.1.
Alopecia Areata Patient-Reported Outcomes 
9.1.2.1.1. Patient Reported Outcomes for Scalp Hair Assessment
Lilly has developed a novel patient-reported outcome (PRO) assessment of the patient’s current 
extent of scalp involvement.  Like the AA-IGA (see Section 9.1.5.), it is comprised of 5 category 
response options:  0 = No missing hair (0% of my scalp is missing hair; I have a full head of 
hair); 1 = A limited area (1% to 20% of my scalp is missing hair); 2 = A moderate area (21% to 
49% of my scalp is missing hair); 3 = A large area (50% to 94% of my scalp is missing hair); and 
4 = Nearly all or all (95% to 100% of my scalp is missing hair). 
9.1.2.1.2. Other Patient Reported Outcomes for Appearance of Eyebrows, 
Appearance of Eyelashes, Eye Irritation, and Nail Appearance
Lilly has developed 4 other novel PRO assessments measuring 3 important AA signs and 
1 important AA symptom: PRO Measure for Eyebrows™, PRO Measure for Eyelashes™, PRO 
Measure for Eye Irritation™, and PRO Measure for Nail Appearance™.  Each of these other 
PRO assessments uses a 4-point response scale, ranging from 0 = normal appearance/no problem 
to 3 = severe appearance/severe problem.

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9.1.2.2.
Other Clinician-Reported Outcomes for Eyebrow Hair Loss Eyelash Hair 
Loss, and Nail Appearance
Lilly has developed 3 other novel clinician-reported outcome (ClinRO) assessments measuring 
3 important AA signs: ClinRO Measure for Eyebrow Hair Loss™, ClinRO Measure for Eyelash 
Hair Loss™, and ClinRO Measure for Nail Appearance™.  Each of these other ClinRO 
assessments uses a 4-point response scale, ranging from 0 = normal appearance/no hair loss to 3 
= severe appearance/severe hair loss.
9.1.3. Health Outcomes and Quality-of-Life Measures
The following patient self-reported questionnaires will be administered via an electronic tablet. 
In other countries, where necessary, the questionnaires have been translated into the native 
language of the region and linguistically validated.
9.1.3.1.
Skindex-16 Adapted for Alopecia Areata (Stage 2 Only)
Skindex-16 has been used to assess the health-related quality of life in patients with skin diseases.  
The Skindex-16 items’ wordings were adapted for use among adults with AA. It is composed of 
16 items grouped under 3 domains:  Symptoms (4 items), Emotions (7 items), and Functioning 
(5 items).  The Skindex-16 Adapted for AA will only be used during Stage 2. 
9.1.3.2.
Medical Outcomes Study 36-Item Short-Form Health Survey Version 2 
Acute
The Short-Form Health Survey (SF-36), Version 2, acute measure is a subjective, generic, 
health-related quality-of-life instrument that is patient-reported and consists of 36 questions 
covering 8 health domains:  physical functioning; bodily pain; role limitations due to physical 
problems; role limitations due to emotional problems; general health perceptions; mental health;
social function; and vitality.  Each domain is scored by summing the individual items and 
transforming the scores into a norm-based T score with higher scores indicating better health 
status or functioning.  In addition, 2 summary scores, the physical component score (PCS) and 
the mental component score (MCS) will be evaluated based on the 8 SF-36 acute domains 
(Maruish 2011).
9.1.3.3.
EQ-5D-5L
The 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/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/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 states of health, as defined by the EQ-5D-5L descriptive system, may 

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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
2015 [WWW]).
9.1.3.4.
Hospital Anxiety and Depression Scale
The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-assessment scale that 
determines the levels of anxiety (7 items) and depression (7 items) that a patient is experiencing 
over the past week.  The HADS utilizes a 4-point Likert response scale (eg, 0 to 3) for each item,
and is intended for ages 12 years to 65 years (Zigmond and Snaith 1983; White et al. 1999).  
Scores for each domain (anxiety and depression) can range from 0 to 21, with higher scores 
indicating greater anxiety or depression (Zigmond and Snaith 1983; Snaith 2003).
9.1.4. Photography
All sites/patients will obtain photographs of the scalp (4 planes), 1 frontal view of the face and 
scalp, and photographs of the eyebrows/eyelashes at Baseline (Week 0, Visit 2).  Photographs of 
nails will be obtained at Baseline (Week 0, Visit 2) from patients with nail involvement 
(ClinRO ≥1) at Baseline, as assessed by the investigator.  In addition, photographs of the scalp 
(4 planes) and 1 photograph (frontal view) of the face and scalp will be obtained at Week 12 
(Visit 5), Week 36 (Visit 8, primary endpoint), Week 52 (Visit 11), and at the ETV if patients 
discontinue prior to Week 52.  Photographs of eyebrows/eyelashes and nails will be obtained at 
Weeks 12, 36, and 52 only from patients with AA involvement (ClinRO ≥1) of these areas at 
Baseline, as assessed by the investigator. Photographs obtained during the study will provide 
qualitative visual evidence of clinical response to treatment with baricitinib for all consenting 
patients.  Photographs will not be used for assessments of efficacy, and missed photographs will 
not be considered a protocol violation.
Camera equipment, necessary ancillary materials, and a study-specific photography manual will 
be provided to all sites by the Sponsor or designee.  The following photographs will be obtained 
by trained site personnel under similar lighting conditions and magnifications, and per 
instructions provided during training and as outlined in the photographic procedure manual:

4-plane views of the scalp, including each side, back, and top of head.

1 frontal view of the face and scalp.

Photographs of the eyebrows/eyelashes will be taken from patients with eyelash and/or 
eyebrow loss (ClinRO Measure for Eyebrow and/or Eyelash Hair Loss ≥1).

A single photograph of each hand will be taken from patients with nail involvement 
(ClinRO Measure for Nail Appearance ≥1).
Photographs are commonly obtained in research investigations of AA and are effective in 
demonstrating disease presentation at Baseline and clinical response following treatment with 
baricitinib.
The photographs may be included in the clinical study report (CSR), a regulatory submission 
package, scientific publications, or in other public dissemination of clinical data to demonstrate 

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disease presentation at Baseline and clinical response following treatment with baricitinib.  
Photographs from consenting patients may also be used in advertising and promotional activities 
including, but not limited to, communication with healthcare professionals/payers, as well as in 
patient education, speaker programs, and digital/print media messaging.
Patient anonymity will be protected in photographs included in patient education, speaker 
programs, print media, or any form available to the public.  To protect the patient’s anonymity, 
identifiable characteristics of the skin, such as faces, birthmarks, or tattoos will be redacted from 
the final photographs and will not appear in any published version of the photograph.  No formal 
analyses of photographs are planned. 
9.1.5. Alopecia Areata – Investigator Global Assessment
The AA-IGA is a categorization of overall scalp hair loss based on the patient’s SALT score, 
which is assigned by the investigator by direct inspection of the patient’s scalp at each visit 
(see Section 9.1.1.1).  The AA-IGA contains 5 categories:  0 = None (SALT score of 0%); 
1 = Limited (SALT score of 1% to 20%); 2 = Moderate (SALT score of 21% to 49%); 3 = Severe 
(SALT score of 50% to 94%); and 4 = Very Severe (SALT score of 95% to 100%).  The AA-
IGA will be automatically derived from the SALT score entered into the electronic clinical 
outcome assessment (eCOA) by the investigator and may be used in exploratory analysis.
9.1.6. Appropriateness of Assessments
All of the clinical and safety assessments in this study are standard, widely used, and generally 
recognized as reliable, accurate, and relevant.  Measurement properties (including reliability and 
validity) of the newly developed single-item assessments (AA-IGA, ClinROs, and PROs
[see Sections 9.1.1 and 9.1.2]) will be evaluated using the Phase 3 trial data.
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 will record all relevant AE/SAE information in the CRF. The Investigator 
remains responsible for following, through an appropriate health care option, AEs that are: 
serious or, otherwise, medically important; considered related to the IP or the study; or that 
caused the patient to discontinue the IP before completing the study.  The patient should be 
followed until the event resolves, 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.

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After the ICF is signed, study site personnel will record, via eCRF, the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs. Investigators should record their assessment of the 
potential relatedness of each AE to IP, via eCRF.
The investigator will interpret and document whether an AE has a reasonable possibility of being 
related to study treatment, to a study device, or to 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 seriousness 
criteria.  The SAE reporting to the Sponsor begins after the patient has signed the ICF and has 
received IP.  However, if an SAE occurs after signing the ICF, but prior to receiving IP, the SAE 
should be reported to the Sponsor, as per SAE-reporting requirements and timelines (see Section 9.2)
if it is considered reasonably possibly related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via 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 

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information.  Patients with a serious hepatic AE should have additional data collected using the 
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 the mother and the fetus.
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient disposition eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to IP or procedure.  United States 21 CFR 
312.32 and European Union Clinical Trial Directive 2001/20/EC and the associated detailed 
guidances or national regulatory requirements in participating countries require the reporting of 
SUSARs.  Lilly has procedures that will be followed for the identification, recording, and 
expedited reporting of SUSARs that are consistent with global regulations and the associated 
detailed guidances.
9.2.2. Adverse Events of Special Interest
Adverse events of special interest will include the following:

infections (including TB, herpes zoster, or opportunistic infections)

malignancies

hepatic events (see Section 9.4.10.1)

major adverse cardiovascular events (MACE) (see Section 9.4.10)

thrombotic events (such as deep vein thrombosis [DVT] and pulmonary embolism [PE]
and arterial thrombotic event [ATE] (see Section 9.4.9).
Sites will provide details on these AEs, as instructed on the eCRF, and may be asked for 
additional description by Lilly.
9.2.3. Complaint Handling
Lilly collects product complaints on IPs and drug delivery systems used in clinical studies in 
order to ensure the safety of study participants, to monitor quality, and to facilitate process and 
product improvements.
Patients will be instructed to contact the investigator as soon as possible if they have a complaint 
or problem with the IP so that the situation can be assessed.

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9.3.
Treatment of Overdose
Refer to the IB.
9.4.
Safety
Any clinically significant findings from ECG testing, physical examination, vital signs 
measurements, or laboratory measurements that result in a diagnosis and that occur after the 
patient receives the first dose of study treatment should be reported to Lilly or its designee as an 
AE via eCRF.
9.4.1. Electrocardiograms
A single 12-lead, standard ECG will be obtained locally at Visit 1 and read by a qualified 
physician (the investigator or qualified designee) at the site to determine whether the patient 
meets entry criteria.
Electrocardiograms may be obtained at additional times, when deemed clinically necessary.
9.4.2. Vital Signs
For each patient, vital signs should be measured according to the SOA (Section 2).
9.4.3. Physical Examination
For each patient, a complete physical examination (excluding pelvic and rectal examinations) 
will be performed at Visit 1 (Screening).  A symptom-directed physical examination will be 
performed at other visits, as specified in the SOA (Section 2).  A complete physical examination 
may be repeated, at the investigator’s discretion, any time a patient presents with physical 
complaints.
9.4.4. Laboratory Tests
For each patient, laboratory tests detailed in Appendix 2 should be conducted according to the 
SOA (Section 2).  Home visits to collect blood and urine samples may be allowed upon written 
approval from the sponsor and if consistent with local regulations.  With the exception of 
laboratory test results that may unblind the study, Lilly or its designee will provide the 
investigator with the results of laboratory tests analyzed by a central vendor, if a central vendor 
is used for the clinical trial.  
9.4.5. Columbia Suicide Severity Rating Scale
The C-SSRS captures the occurrence, severity, and frequency of suicidal ideation and/or 
behavior during the assessment period.  The scale includes suggested questions to solicit the type 
of information needed to determine if suicidal ideation and/or behavior occurred.  The C-SSRS is 
administered by an appropriately trained healthcare professional with at least 1 year of patient 
care/clinical experience.  The tool was developed by the National Institute of Mental Health trial 
group for the purpose of being a counterpart to the Columbia Classification Algorithm of Suicide 
Assessment categorization of suicidal events.  For this study, the scale has been adapted (with 

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permission from the scale authors) to include only the portion of the scale that captures the 
occurrence of the 11 preferred ideation and behavior categories.
The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS, but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
9.4.6. Self-Harm and Follow-Up Supplement Forms
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the self-harm follow-up form.  The self-harm 
follow-up form is a series of questions that provides a more detailed description of the behavior 
cases.
9.4.7. Chest X-Ray and Tuberculosis Testing
A posterior–anterior view chest x-ray will be obtained locally at Screening (Visit 1), unless one 
has been performed in the past 6 months and the x-ray and/or the report is available.  The chest 
x-ray will be reviewed by the investigator or his/her designee to exclude patients with active TB 
infection.  In addition, patients will be tested at screening (Visit 1) for evidence of active or 
latent TB, as described in the Exclusion Criteria, Section 6.2.
Investigators should follow local guidelines for monitoring patients for TB if a patient is at high 
risk for acquiring TB or reactivation of latent TB.
9.4.8. Hepatitis B Virus DNA Monitoring
Hepatitis B virus DNA testing will be performed in enrolled patients who tested positive for 
HBcAb at screening.  
Patients who are HBcAb positive and HBV DNA negative (undetectable) at screening (Visit 1) 
will require measurement of HBV DNA approximately every 3 months during treatment (as 
detailed in the SOA [Section 2]) and at the follow-up visit (V801), regardless of their hepatitis B 
surface antibody (HBsAb) status.
The following actions should be taken in response to HBV DNA test results:

If a single result is obtained with a value “below limit of quantitation,” the test should 
be repeated within approximately 2 weeks.  

If the repeat test result is “target not detected,” monitoring will resume according to 
the study schedule.  

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
If the patient has 2 or more test results with a value “below limit of quantitation,” 
HBV DNA testing should be performed approximately once per month for the 
remainder of the study, and referral to a hepatologist is recommended.
Note: Unscheduled visits may be used to monitor HBV DNA monthly.

If a result is obtained with a value above the limit of quantitation at any time during 
the study, the patient will be permanently discontinued from IP (see Section 8.1.1),
and should be referred to a hepatology specialist.  
o
In selected cases, investigators may temporarily continue IP in accordance 
with current immunomodulator management in the setting of HBV DNA 
positivity.  This option may be considered in consultation with Lilly (or its 
designee) and evaluation of individual patient risks and benefits.
9.4.9. Venous Thromboembolism Assessment
If a patient develops the signs and symptoms of a DVT or PE, appropriate local laboratory tests 
and imaging should be performed, as necessary, for diagnosis of the event.  For confirmed cases, 
additional laboratory testing may be performed, as outlined in Appendix 7. 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.  All suspected VTE events will be independently 
adjudicated by a blinded Clinical Event Committee (see Section 10.3.7.4).
9.4.10. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, only members of the data monitoring committee (DMC), an advisory group for 
this study formed to protect the integrity of data, can conduct additional analyses of the safety 
data (refer to Interim Analyses section [Section 10.3.7]).
The Lilly CRP will monitor safety data throughout the course of the study.  Lilly will review 
SAEs within timeframes mandated by company procedures.  The Lilly CRP will, as is 
appropriate, consult with the functionally independent Global Patient Safety (GPS) therapeutic 
area physician or clinical scientist and periodically review trends in safety data and laboratory 
analytes.  Any concerning trends in frequency or severity noted by an investigator and/or Lilly 
(or 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 GPS will be unblinded for regulatory reporting 
and safety monitoring purposes.  These measures will preserve the integrity of the data collected 
during this trial and minimize any potential for bias while providing for appropriate safety 
monitoring.

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Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular events and VTEs.  Adverse event reports and vital signs will be collected at each 
study visit.  The cardiovascular monitoring plan includes the following:

regular monitoring of lipid levels

potential MACE (cardiovascular death, myocardial infarction, stroke), other 
cardiovascular events, such as hospitalization for unstable angina, hospitalization for 
heart failure, serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary 
revascularization (eg, coronary artery bypass graft or percutaneous coronary 
intervention), venous and arterial thrombotic events, and noncardiovascular deaths will 
be identified by the investigative site or through medical review and will be sent to a 
blinded Clinical Event Committee for adjudication at regular intervals.
9.4.10.1. Hepatic Safety Monitoring
If a study patient experiences elevated ALT ≥3 × ULN, ALP ≥2 × ULN, or elevated TBL 
≥2 × ULN, liver testing (Appendix 4) should be repeated within 3 to 5 days, including ALT, 
AST, ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm 
the abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor.  Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate Baseline levels. 
Discontinuation criteria of IPs, either temporary interruption or permanent discontinuation, due 
to abnormal ALT, AST, TBL, or ALP, are detailed in Section 8.1.
Hepatic Safety Data Collection
Additional safety data should be collected via the hepatic eCRF if 1 or more of the following 
conditions occur: 

elevation of serum ALT to ≥5 × ULN on 2 or more consecutive blood tests

elevated serum TBL to ≥ 2 × ULN (except for cases of known Gilbert’s syndrome)

elevation of serum ALP to ≥2 × 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 Appendix 4 and Appendix 5 for a description of hepatic laboratory values that warrant 
patient exclusion from the study, temporary or permanent discontinuation of IP, or additional 
safety collection via the hepatic eCRF.
9.5.
Pharmacokinetics
A single venous blood sample will be drawn at the visits and times indicated below.  These blood 
samples will be used to determine the plasma concentrations of baricitinib using a validated 
liquid chromatography tandem mass spectrometry method.  Blood samples that will be used for 

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other laboratory assessments (eg, chemistry, hematology) may be drawn at approximately the 
same time as the samples drawn to determine plasma concentrations of baricitinib, with the 
exception of Week 0, which requires specific postdose sampling times.  The inability to collect a 
PK sample will not be considered a protocol violation.  The timing will be as follows:

At Visit 2 (Week 0), patients will take their IP in the clinic, and PK samples will be drawn 
15 minutes and 1 hour postdose.  Samples for the other clinical laboratory assessments must 
be drawn prior to receiving the first dose.

At Visit 3 (Week 4), patients will be asked to take their IP at home prior to visiting the clinic.  
The clinic visit should be scheduled so that the blood sample collected during this visit is 
drawn 2 to 4 hours after the dose is taken at home.

At Visit 4 (Week 8), patients will be asked to take their IP at home prior to visiting the clinic.  
The clinic visit should be scheduled so that the blood sample collected during this visit is 
drawn 4 to 6 hours after the oral dose is taken at home.

For Visit 5 (Week 12), and Visit 6 (Week 16), patients will be asked to NOT take their IP 
before visiting the clinic, and a blood sample will be collected at any time predose on the day 
of the clinic visits.  If the patient has taken the oral dose prior to the visit, the sample may be 
drawn anytime postdose, and the inability to collect a predose sample will not be considered 
a protocol violation.

For an ET prior to Visit 6 (Week 16), a sample may be drawn anytime if the last dose of IP 
was taken within the last 48 hours.  After Week 16, if the ET is due to an AE, then a sample 
should be drawn if the last dose of IP was taken within the last 48 hours of the ET at or 
before Visit 24 (Week 200). 

In the event of an SAE, up to 2 additional blood samples may be taken at the investigator’s 
discretion.  If collected, the PK samples should be collected after the reported event, 
approximately 6 hours apart and within 24 hours of the patient’s last dose.
For visits where PK samples will be collected, the actual date and 24-hour clock time of sample 
collection, and the date and time of the 2 doses prior to the sample being drawn, should be 
recorded.  For Visits 3 and 4, these 2 doses should be the dose given the morning of the day of 
sample collection and the dose given the previous day.  For Visits 5 and 6, these 2 doses should 
be the dose given the day before the visit and the dose given the day before that. 
This sampling schedule should be followed as closely as possible; however, failure to take PK 
samples at these specified times will not be considered a protocol violation.  If the patient fails to 
follow the directions for a particular visit, the sample should still be collected at that visit, and 
the date and 24-hour clock time of sample collection and the date and 24-hour clock time of the 
2 doses prior to the sample being drawn should be recorded.

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Pharmacokinetic samples from patients receiving baricitinib will be assayed; samples from 
patients receiving placebo may not be assayed.  Pharmacokinetic samples will be kept in storage 
at a laboratory facility designated by the Sponsor.  Pharmacokinetic samples may also be assayed 
for additional exploratory analyses.  Pharmacokinetic results will not be provided to investigative 
sites until the completion of the study or to the blinded study team until the study has been 
unblinded.  
Bioanalytical samples collected to measure IP concentration will be retained for a maximum of 
1 year following last patient visit for the study.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenomics
9.7.1. Whole Blood Samples for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis, as specified in the SOA 
(Section 2), where local regulations allow.  
Samples will not be used to conduct unspecified disease or population genetic research, either 
now or in the future.  Samples will be used to investigate variable response baricitinib and to 
investigate genetic variants thought to play a role in AA.  Assessment of variable response may 
include evaluation of AEs or differences in efficacy. 
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained at a facility selected by Lilly for a maximum of 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and/or ethical review boards 
(ERBs)/investigational review boards (IRBs) impose shorter time limits.  This retention period 
enables use of new technologies, response to regulatory questions, and investigation of variable 
response that may not be observed until later in the development of baricitinib or after baricitinib 
become(s) commercially available.
Molecular technologies are expected to improve during the 15-year storage period and, therefore,
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome-wide association studies, and candidate gene studies.  Regardless of 
technology utilized for genotyping, data generated will be used only for the specific research 
scope described in this section. 
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics (PD), mechanism of action, variability of patient response 
(including safety), and clinical outcome.  Sample collection is incorporated into clinical studies 

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to enable examination of these questions through measurement of biomolecules including DNA, 
RNA, proteins, lipids, and other cellular elements.
Blood samples for biomarker research will be collected at the times specified in the SOA 
(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 AA, mechanism of action of baricitinib, and/or research 
method or in validating diagnostic tools or assay(s) related to AA.  
All samples will be coded with the patient number.  These samples, and any data generated, can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained at a facility selected by Lilly for a maximum 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and ERBs impose shorter 
time limits.  This retention period enables use of new technologies, response to regulatory 
questions, and investigation of variable response that may not be observed until later in the 
development of baricitinib or after baricitinib becomes commercially available.
9.9.
Medical Resource Utilization and Health Economics
Health economics will be evaluated in this study utilizing the EQ-5D-5L (see Section 9.1.3).  
Medical resource utilization parameters will not be evaluated in this study.

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10. Statistical Considerations
10.1. Sample Size Determination
Study JAHO will screen approximately 1035 patients in order to enroll approximately 
725 patients over Stage 1 and Stage 2.  Stage 1 aims to enroll a maximum of approximately 
300 patients with the first approximately 100 patients randomized in a 1:1:1:1 ratio to placebo 
QD, baricitinib 1-mg QD, baricitinib 2-mg QD, or baricitinib 4-mg QD and up to a maximum of 
an additional 200 patients randomized in a 2:2:3 ratio to placebo QD, baricitinib 2-mg QD, or
baricitinib 4-mg QD.  This sample size will yield approximately 100 randomized and treated 
Phase 2 patients who will have completed Week 12 (Visit 5) or discontinued early, and who will 
be used for the conduct of the Phase 2, Week 12 interim analysis.  The goal of this interim 
analysis is to select up to 2 doses of baricitinib or to stop for futility based on pre-specified 
criteria. The sample size of approximately 100 patients is also sufficient to select at least one
efficacious dose at least 80% of the time, based on the said pre-specified criteria.
Stage 2 randomization will begin with a 2:2:3 ratio for placebo QD, baricitinib 2-mg QD, or
baricitinib 4-mg QD after Decision Point.  This study is designed so that approximately 
425 patients are randomized in Stage 2.  All randomized patients in the Phase 3 portion will be 
included in the primary efficacy analysis.  Hence, approximately 625 patients will be eligible for 
the primary efficacy analysis.  This sample size will provide more than 90% power to test the 
superiority of baricitinib 4-mg to placebo or the superiority of baricitinib 2-mg to placebo in the 
primary endpoint (the proportion of patients achieving SALT ≤20 at Week 36) based on a 2-
sided Fisher exact test within the graphical testing scheme, at an initial significance level of 0.04 
for baricitinib 4-mg and 0.01 for baricitinib 2-mg. The assumptions used for the power 
calculation are as follows: 30% response rate for baricitinib 4-mg, 20% response rate for 
baricitinib 2-mg, and 5% response rate for placebo (Kennedy Crispin et al. 2016; Mackay-
Wiggan et al. 2016). The initial alpha allocation may be adjusted in the SAP when newer 
information is obtained on the endpoints that are being tested and will be finalized prior to the 
primary database lock.
Patients who achieve SALT ≤20 at Week 52 (responders) AND who have remained on the same 
dose of baricitinib from randomization (Visit 2) to Week 52, will enter the randomized 
withdrawal, which is meant to evaluate the change in clinical response after treatment 
withdrawal, and does not account for whether the sample size is sufficient to detect statistical
difference between baricitinib and placebo. It is expected that there will be approximately 
100 patients eligible for the randomized withdrawal. 

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10.2. Populations for Analyses
For the purpose of analyses, the following populations are defined:
Population
Description
Phase 2, Week 12 Interim 
Analysis Set (IAS)
The first approximately 100 randomized and treated patients in Phase 2 portion 
within Stage 1 who completed Visit 5 (Week 12) assessment or discontinued 
early.  Patients will be analyzed according to the IP to which they were 
randomized at Baseline (Visit 2).
Phase 2, Week 36 Interim 
Analysis Set (IAS)
The first approximately 100 randomized and treated patients in Phase 2 portion 
within Stage 1 who completed Visit 8 (Week 36) assessment or discontinued 
early.  Patients will be analyzed according to the IP to which they were 
randomized at Baseline (Visit 2).
Full Analysis Set (FAS) 
All patients enrolled in Phase 3 portion, and who are randomized to baricitinib 
4-mg, baricitinib 2-mg, and placebo treatment arms in both Stages 1 and 2 will 
be included in the FAS.  Patients will be analyzed according to the IP to which 
they were randomized at Baseline (Visit 2).
Modified Full Analysis Set
(mFAS) Population 
All patients enrolled in Phase 3 portion, and who are randomized to baricitinib 
4-mg, baricitinib 2-mg, and placebo treatment arms in both Stages 1 and 2, and 
received at least 1 dose of IP, will be included in the mFAS. It excludes patients 
with female pattern baldness and male patients with diffuse AGAa (Grade IV 
and above) (Norwood 1975) identified at Week 36.  Patients will be analyzed 
according to the IP to which they were randomized at Baseline (Visit 2).
Per-Protocol Set (PPS)
The PPS will include all mFAS patients who are not deemed noncompliant with
treatment, who do not have any of the important protocol deviations that 
exclude patients from the PPS, and whose investigator site does not have 
significant GCP deviations that require a report to regulatory agencies.  The 
important protocol deviations, including the subset that result in exclusion from 
the PPS, will be determined while the study team remains blinded, prior to the 
primary outcome database lock.
Safety Population 
The safety population is defined as all randomized patients who receive at least 
1 dose of investigational product (IP) and who did not discontinue from the 
study for the reason ‘Lost to Follow-up’ at the first postbaseline visit.  Patients 
will be analyzed according to the treatment group to which they were assigned. 
Abbreviations:  AGA = androgenetic alopecia; GCP = good clinical practice; IP = investigational product.
a
Some male patients with Grade IV AGA and female patients with patterned baldness may only be identified after 
hair regrowth on the scalp.
Any additional analysis populations will be defined in the SAP.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly. 
The interim analysis at the Decision Point would be conducted in the Phase 2, Week 12 IAS 
population. A second interim analysis will be conducted using the Phase 2, Week 36 IAS 
population. The efficacy analysis of the primary and key secondary endpoints in the Phase 3 

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portion will be conducted in the FAS population.  All other efficacy analyses will be conducted 
in the FAS population or other populations described in the SAP.  Safety analyses will be 
conducted using the safety population.  Additional efficacy or safety interim analyses prior to the 
final database lock (F-DBL) may occur to support regulatory submissions and will be described 
in the SAP.
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05 unless, otherwise,
stated.
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 CSR.  Additional exploratory analyses of the data will be conducted, as deemed 
appropriate.  Complete details of the planned analyses will be documented in the SAP.
10.3.1.1. Analysis Methods
The primary analysis of discrete efficacy and health outcomes variables will use a logistic 
regression analysis with geographic region, duration of current episode at Baseline (<4 years vs 
≥4 years), baseline value, and treatment group in the model unless, otherwise, stated.  The p-
value and 95% confidence interval (CI) for the odds ratio from the logistic regression model are 
used for primary statistical inference. In the case when logistic regression model does not 
produce statistical results due to sparse data, Fisher exact test will be used. The difference in 
percentages and 95% CI of the difference in percentages using the Newcombe-Wilson method 
without continuity correction are used for descriptive purposes unless, otherwise, specified.  
Missing data will generally be imputed using NRI, as described in Section 10.3.1.2.
The primary analyses for the continuous efficacy and health outcome variables will use 
ANCOVA with geographic region, duration of current episode at Baseline (<4 years vs ≥4 years), 
treatment group, and baseline value in the model unless, otherwise, stated. Type III tests for the 
least-squares (LS) means will be used for statistical comparison between treatment groups. The 
LS mean difference, standard error, p-value, and 95% CI will also be reported. The method used 
to handle missing data will be modified last observation carried forward (mLOCF) and is 
reasonable for this data as very few patients experienced waxing and waning in scalp hair during 
the course of treatment from the Phase 2 portion and several external studies on alopecia areata. 
Additional details of the mLOCF method are described in Section 10.3.1.2.
Analysis of continuous efficacy and health outcome variables over time may be made using a 
restricted maximum likelihood-based mixed model for repeated measures (MMRM) analysis.  
The model will include geographic region, duration of current episode at Baseline (<4 years vs 
≥4 years), treatment group, visit, treatment-by-visit interaction as fixed categorical effects, and 
baseline value/baseline value-by-visit interaction as fixed continuous effects unless, otherwise, 
stated.  An unstructured covariance structure will be used to model the between- and within-
patient errors.  If this analysis fails to converge, the heterogeneous autoregressive [ARH(1)], 
followed by the heterogeneous compound symmetry (CSH), followed by heterogeneous Toeplitz
(TOEPH) will be used.  The variance-covariance structure that results in the smallest Akaike 

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information criterion will be used.  The Kenward-Roger method will be used to estimate the 
denominator degrees of freedom.  Type III tests for the LS means will be used for the statistical 
comparisons.  The LS mean difference, standard error, p-value, and CIs will also be reported.  
Contrasts will be set up within the model to test treatment groups at specific time points of 
interest. Additional details of the MMRM method are described in Section 10.3.1.2.
Time-to-event analysis will be performed and analyzed using log-rank test. A Cox proportional 
hazards model may be used with treatment and other stratification variables in the model unless, 
otherwise, stated.  Hazard ratio with CIs may be reported.  Kaplan–Meier curves will also be 
produced.  Diagnostic tests for checking the validity of the proportional hazards assumption may 
be performed, and these would be described in detail in the SAP.  If the assumption of 
proportional hazards is not justified, nonproportionality may be modeled by stratification.
The Fisher exact test will be used to perform any between-treatment group comparisons for AEs, 
discontinuations, and other categorical safety data.  Continuous vital signs, body weight, and 
other continuous safety variables, including laboratory variables, will be analyzed using an 
ANCOVA with treatment and baseline value in the model.  Type III tests will be used for 
statistical comparison between treatment groups.  Shift tables for categorical safety analyses (eg,
“high” or “low” laboratory results) will also be produced.
10.3.1.2. Missing Data Imputation
As with any clinical study, patient dropouts and consequently missing data is an expected issue 
for this study.  Patients who discontinue treatment, unless they withdraw consent, will be 
encouraged to remain in the study and follow the scheduled visits until the primary analysis 
timepoint at Week 36 to provide the efficacy and safety data needed.  While every effort will be 
made to reduce missing data, the missing data imputation methods described below will be used 
to provide a conservative approach for assessing efficacy endpoints when patients have missing 
data.  
The following imputation rules will be used for the double-blind treatment period (Period 2).  
Details for handling missing data in later periods will be provided in the SAP.

Non-responder Imputation:  Analysis of categorical efficacy and health outcomes variables 
will be assessed using NRI unless, otherwise, stated.  Patients will be considered 
nonresponders for the NRI-based analysis if they do not meet clinical response criteria or if 
they permanently discontinued study treatment or discontinued from the study at any time 
prior to the timepoint of interest for any reason.  An additional analysis may be performed on 
all available data up to permanent treatment discontinuation. 

Modified last observation carried forward:  For continuous variables, the primary analysis 
will be ANCOVA with missing data imputed by the mLOCF method, which uses the most 
recent non-missing post-baseline assessment. The specific modification to the LOCF is data 
after permanent study treatment discontinuation will not be carried forward.  

Mixed model for repeated measures:  For continuous variables, an MMRM analysis with a 
missing at random assumption for handling missing data may also be conducted.  This 
analysis takes into account both the missingness of data and the correlation of the repeated 

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measurements.  No additional imputation methods will be applied to the MMRM analysis.  
For patients who permanently discontinue the study or the study treatment, data after 
discontinuation will be excluded.  
Additional analyses, including additional methods for handling missing data, such as placebo 
multiple imputation (pMI) and tipping point analysis, are specified in Appendix 6 and finalized 
details (if necessary) may be included in the SAP. 
10.3.1.3. Multiple Comparisons/Multiplicity
This study uses an operationally seamless adaptive Phase 2/3 study design.  Data collected from 
the additional approximately 200 patients enrolled in Stage 1 and all patients enrolled in Stage 2 
will remain blinded, and the FAS population will be used for the primary efficacy analysis.  
Pre-specified changes in randomization ratio and allocation to selected doses into Stage 2 will be 
triggered only through IWRS.  Hence, the Type I error rate for the primary efficacy analysis is 
controlled at a 2-sided alpha level of 0.05.
Multiplicity adjusted analyses will be performed on the primary and key secondary objectives in 
order to control the overall family-wise Type I error rate at a 2-sided alpha level of 0.05. The 
graphical multiple testing procedure described in Bretz et al. (2011) will be used.  The graphical 
approach is a closed testing procedure; hence, it strongly controls the familywise error rate 
across all endpoints (Alosh et al. 2014).  Figure JAHO.3 illustrates the graphical testing 
procedures that will be used; a summary of the procedures is provided in Appendix 6.  Details of 
the specific graphical testing scheme (including testing order, interrelationships, Type I error 
allocation for the primary and key secondary endpoints, and the associated propagation) will be 
pre-specified in Appendix 6 and the SAP.  These details may be revised in the SAP when newer 
information is obtained on the endpoints that are being tested.  However, the graphical testing 
scheme will be finalized prior to primary database lock.

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Figure JAHO.3.
Graphical testing procedure for I4V-MC-JAHO.
The following is a list of primary and key secondary hypotheses to be tested.  The subscript for 
H denotes the selected 2 doses, the numerical identifier of the endpoint within the dose, and the 
type of hypothesis (0 for null, 1 for alternative), respectively.

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Primary Null Hypothesis:

H1,1,0:  Proportion of patients in the baricitinib 4-mg dose group achieving SALT ≤20 at 
Week 36 is less than or equal to placebo.

H2,1,0:  Proportion of patients in the baricitinib 2-mg dose group achieving SALT ≤20 at 
Week 36 is less than or equal to placebo.
Key Secondaries Null Hypotheses:

H1,2,0:  Proportion of patients in the baricitinib 4-mg dose group with a PRO for Scalp 
Hair Assessment score of 0 or 1 with a ≥2-point improvement at Week 36 is less than or 
equal to placebo (among patients with a score of ≥3 at baseline).

H2,2,0:  Proportion of patients in the baricitinib 2-mg dose group with a PRO for Scalp 
Hair Assessment score of 0 or 1 with a ≥2-point improvement at Week 36 is less than or 
equal to placebo (among patients with a score of ≥3 at baseline).

H1,3, 0:  Proportion of patients in the baricitinib 4-mg dose group achieving SALT ≤20 at 
Week 24 is less than or equal to placebo.

H2,3, 0:  Proportion of patients in the baricitinib 2-mg dose group achieving SALT ≤20 at 
Week 24 is less than or equal to placebo.

H1,4,0:  Proportion of patients in the baricitinib 4-mg dose group achieving SALT ≤20 at 
Week 16 is less than or equal to placebo.

H2,4,0:  Proportion of patients in the baricitinib 2-mg dose group achieving SALT ≤20 at 
Week 16 is less than or equal to placebo.

H1,5,0:  Proportion of patients in the baricitinib 4-mg dose group achieving an absolute 
SALT score ≤10 at Week 36 is less than or equal to placebo.

H2,5,0:  Proportion of patients in the baricitinib 2-mg dose group achieving an absolute 
SALT score ≤10 at Week 36 is less than or equal to placebo.

H1,6,0:  Proportion of patients in the baricitinib 4-mg dose group achieving an absolute 
SALT score ≤10 at Week 24 is less than or equal to placebo.

H2,6,0:  Proportion of patients in the baricitinib 2-mg dose group achieving an absolute 
SALT score ≤10 at Week 24 is less than or equal to placebo.

H1,7,0:  Proportion of patients in the baricitinib 4-mg dose group with a SALT90 at 
Week 36 is less than or equal to placebo.

H2,7,0:  Proportion of patients in the baricitinib 2-mg dose group with a SALT90 at 
Week 36 is less than or equal to placebo.

H1,8,0:  Proportion of patients in the baricitinib 4-mg dose group with a SALT50 at 
Week 12 is less than or equal to placebo.

H2,8,0:  Proportion of patients in the baricitinib 2-mg dose group with a SALT50 at 
Week 12 is less than or equal to placebo.

H1,9,0:  Proportion of patients in the baricitinib 4-mg dose group achieving ClinRO 
Measure for EB Hair Loss 0 or 1 with ≥2-point improvement from baseline at Week 36 is 
less than or equal to placebo (among patients with ClinRO Measure for EB Hair Loss ≥2 
at Baseline)

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
H2,9,0:  Proportion of patients in the baricitinib 2-mg dose group achieving ClinRO
Measure for EB Hair Loss 0 or 1 with ≥2-point improvement from baseline at Week 36 is 
less than or equal to placebo (among patients with ClinRO Measure for EB Hair Loss ≥2 
at Baseline)

H1,10,0:  Proportion of patients in the baricitinib 4-mg dose group achieving ClinRO 
Measure for EL Hair Loss 0 or 1 with ≥2-point improvement from baseline at Week 36 is 
less than or equal to placebo (among patients with ClinRO Measure for EL Hair Loss ≥2 
at Baseline)

H2,10,0:  Proportion of patients in the baricitinib 2-mg dose group achieving ClinRO 
Measure for EL Hair Loss 0 or 1 with ≥2-point improvement from baseline at Week 36 is 
less than or equal to placebo (among patients with ClinRO Measure for EL Hair Loss ≥2 
at Baseline)

H1,11,0: Percent change from Baseline in SALT score of patients in the baricitinib 4-mg
dose group at Week 36 is greater than or equal to placebo.

H2,11,0:  Percent change from Baseline in SALT score of patients in the baricitinib 2-mg
dose group at Week 36 is greater than or equal to placebo.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
A detailed description of patient disposition by treatment will be summarized with reasons for 
discontinuation.  Frequency counts and percentages will be presented for each treatment group.  
All patients who discontinue from the study or the study treatment will be identified, along with 
their reason for discontinuation. 
10.3.2.2. Patient Characteristics
Demographic and Baseline characteristics will be summarized descriptively by treatment group.  
Descriptive statistics including number of patients, mean, standard deviation, median, minimum, 
and maximum will be provided for continuous measures, and frequency counts and percentages 
will be tabulated for categorical measures.  No formal statistical comparisons will be made 
among treatment groups unless, otherwise, stated.  A complete list of patient characteristics and 
Baseline clinical measures will be provided in the SAP.
10.3.2.3. Concomitant Therapy
Concomitant medications will be descriptively summarized by treatment group in terms of 
frequencies and percentages using the IAS population for the Phase 2 portion and FAS
population for the Phase 3 portion.  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 IP tablets.  A patient will be considered significantly 
noncompliant if he/she misses more than 20% of the prescribed doses during the study, unless 
the patient’s IP is withheld by the investigator for safety reasons (i.e., compliance <80%).  
Similarly, a patient will be considered significantly noncompliant if he/she is judged by the 
investigator to have intentionally or repeatedly taken more than the prescribed amount of 

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medication (i.e., compliance ≥120%).  Patients who are significantly noncompliant will be 
excluded from the per-protocol set (PPS) (see Section 10.2).
10.3.3. Efficacy Analyses
10.3.3.1. Primary Analyses
The primary efficacy measure is the binary outcome of response defined as SALT ≤20 (see 
Section 9.1.1) at Week 36.  The primary analysis testing the treatment difference between 
baricitinib 4-mg and placebo or baricitinib 2-mg and placebo will be conducted using a logistic 
regression model, as described in Section 10.3.1.1. In the case when logistic regression model 
does not produce statistical results due to sparse data, Fisher exact test will be used. 
As mentioned in Section 10.3.1.3, Type I error is controlled at 0.05 level because no data that is 
used in the interim analyses will be included in the primary efficacy analysis.  The NRI method 
will be used for missing data, as described in Section 10.3.1.2, as it is a conservative imputation 
approach for handling missing data for patients who permanently discontinued study treatment or 
discontinued from the study before primary endpoint due to reasons other than lack of efficacy 
(e.g., lost to follow-up).
Additional analysis of the primary efficacy outcome may be conducted and include analyzing all 
available data up to the permanent treatment discontinuation. 
10.3.3.2. Secondary Analyses
Treatment comparisons in the proportion of patients achieving a binary response will be 
analyzed using the logistic regression model defined in Section 10.3.1.1. In the case when 
logistic regression model does not produce statistical results due to sparse data, Fisher exact test 
will be used. For binary responses, missing data will be imputed using the NRI method 
described in Section 10.3.1.2 unless, otherwise, stated.  Treatment comparisons in the continuous 
measures will be analyzed using the ANCOVA method defined in Section 10.3.1.1 unless, 
otherwise, specified.  Time-to-event data will be analyzed using log-rank test along with Kaplan-
Meier curves.  
Additional analysis of the secondary efficacy outcome may be conducted and include analyzing 
all available data up to the permanent treatment discontinuation. 
10.3.3.3. Exploratory Analyses 
Analyses will be conducted for the other exploratory objectives defined in Section 4.  Specific 
details of analyses will be specified in the SAP.
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 are defined as AEs that first occurred or worsened in 
severity after the first dose of study treatment.  The number of TEAEs, as well as the number and 
percentage of patients who experienced at least 1 TEAE, will be summarized using the Medical 
Dictionary for Regulatory Activities (MedDRA) for each system organ class (or a body system) 

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and each preferred term by treatment group.  Serious adverse events and AEs that lead to 
discontinuation of IP will also be summarized by treatment group.  The Fisher exact test will be 
used to perform comparisons between each baricitinib dose and the placebo group.
All clinical laboratory results will be descriptively summarized by treatment group.  Individual 
results that are outside of normal reference ranges will be flagged in data listings.  Quantitative 
clinical hematology, chemistry, and urinalysis variables obtained at the Baseline to postbaseline 
visits will be summarized as changes from Baseline by treatment group and analyzed using 
ANCOVA with treatment and baseline value in the model.  Categorical variables, including the 
incidence of abnormal values and incidence of AEs of special interest, will be summarized by 
frequency and percentage of patients in corresponding categories.  Shift tables will be presented 
for selected measures.
Observed values and changes from Baseline for vital signs and physical characteristics will be 
descriptively summarized by treatment group and timepoint. Change from Baseline in vital signs 
and body weight will be analyzed using ANCOVA with treatment and baseline value in the 
model. 
Summary tables or listings for the C-SSRS and the Self-Harm and Follow-Up Supplement Forms
will be produced, as needed.
The incidence and average duration of IP interruptions will be summarized and compared 
descriptively among treatment groups.  Various techniques may be used to estimate the effects of 
IP interruptions on safety measures.  Further analyses may be performed and will be planned in 
the SAP.
Full details of the safety analyses and any derivations of AEs of special interest will be 
documented in the program safety analysis plan and study SAP.
10.3.5. Pharmacokinetic Analyses
All plasma baricitinib concentration-time data will be pooled and evaluated using population PK 
methods.  A covariate screen of patient and study-specific factors will be included in the 
analyses, based on factors investigated in previous and (if any) ongoing PK analyses, and on 
their relevance to the target population.  Exploratory and/or model-based analyses examining the 
relationships between baricitinib exposure and efficacy and response endpoints will be 
conducted.  Other analyses of efficacy and safety outcome measures may also be assessed, as 
scientifically appropriate and warranted by available data.  Details about the analyses to be 
conducted will be contained in the PK/PD analysis plan.
10.3.6. Other Analyses
10.3.6.1. Subgroup Analyses 
To assess whether the treatment effect is similar across subgroups for the primary efficacy 
outcome, a logistic model will be used and will include treatment, baseline value, stratification 
variables, the subgroup variable (eg, sex), and the subgroup-by-treatment interaction.  If the 

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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.
Subgroups to be evaluated will include: demographic characteristics (such as region or country, 
gender, age, race), renal function, and Baseline disease characteristics.  Additional subgroups, as 
well as detailed descriptions of the subgroup variables, will be defined in the SAP.
Further definitions for the levels of the subgroup variables, the analysis methodology, and any 
additional subgroup analyses will be defined in the SAP.  Because this study is not adequately 
powered for subgroup analyses, subgroup analyses will generally be treated as exploratory. 
10.3.7. Interim Analyses
10.3.7.1. Decision Point Committee
A Decision Point will occur when first approximately 100 randomized and treated patients have 
completed their assessments at Week 12 (Visit 5) or discontinued early.  At the Decision Point, a 
Decision Point Committee will review efficacy and safety data and provide a recommendation, 
based on pre-specified criteria, for which up to 2 doses will advance into Stage 2 or to 
recommend not to proceed to Stage 2 for futility.  If the study continues into Stage 2, the study 
sites will be informed of the selected baricitinib doses.  The study team will also be informed of 
the selected doses to trigger the conduct of an additional Phase 3 trial, Study JAIR. 
Because data collection from patients in Phase 2 portion will still be ongoing, even after the 
Decision Point, information that may unblind the patients during and after the analyses will not 
be reported to study sites or blinded study team until the study is complete.  Additionally, all 
randomized patients in Stage 1, other than those enrolled in Phase 2 portion, will remain blinded.  
These patients will be combined with patients in Stage 2 for primary efficacy analysis. 
Unblinding and operation of the Decision Point Committee details will be specified in a separate 
unblinding plan document.
10.3.7.2. Data Monitoring Committee
A DMC will oversee the conduct of this trial.  The DMC will consist of members external to 
Lilly.  This DMC will follow the rules defined in the DMC charter, focusing on potential and 
identified risks for this molecule and for this class of compounds.  Data Monitoring Committee 
membership will include, at a minimum, specialists with expertise in dermatology, statistics, and 
other appropriate specialties.
The DMC will be authorized to review unblinded results of analyses by treatment group prior to 
final database lock, including study discontinuation data, AEs/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 
study will not be stopped for positive efficacy results.  Details of the DMC will be documented 
in a DMC charter and DMC analysis plan.

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The DMC is authorized to evaluate unblinded interim efficacy and safety analyses during both
stages of the study, whereas the Decision Point Committee will only review efficacy and safety 
data of the Phase 2 portion of Stage 1 and will be blinded to all data that will be used in Phase 3.  
Study sites will receive information about interim results if they need to know for the dose 
change or safety of their patients.
Unblinding details will be specified in a separate unblinding plan document.
10.3.7.3. Other Interim Analyses
10.3.7.3.1.Phase 2 Week 36 Interim Analysis
When all patients enrolled in the Phase 2 portion will have completed their assessments at Week 
36 (Visit 8) or discontinue early, a second interim analysis of the Phase 2 portion will take place.  
Unblinding details will be specified in a separate unblinding plan document
This Phase 2 Week 36 interim analysis may trigger an interim analysis of the Phase 3 portion, 
before the primary outcome database lock (PO-DBL), for evaluation of futility. 
10.3.7.3.2.Week 36 Primary Outcome Analysis and Other Regulatory Submission 
Activities

After all randomized patients in the Phase 3 portion complete the primary efficacy 
assessment at Week 36 (Visit 8) or discontinue early, the database will be locked and data 
will be unblinded to a limited number of pre-identified individuals to initiate work for 
submission. Although it is called an interim analysis with respect to the entire Phase 3
population, the primary outcome database lock (PO-DBL) interim analysis is the only 
and final analysis for the primary endpoint. Therefore, no alpha adjustment for this 
interim analysis is planned. 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.

Besides the Decision Point Committee and 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 PO-DBL, to initiate the final population PK/PD model 
development processes or to initiate work for regulatory submission.

Another interim analysis will occur for the 3-4-month safety update database lock.

Additional efficacy or safety interim analyses prior to the final database lock (F-DBL)
may occur to support regulatory submissions and scientific disclosures.
If an unplanned interim analysis is deemed necessary, the appropriate Lilly medical director or 
designee will be consulted to determine whether it is necessary to amend the protocol.
10.3.7.4. Adjudication Committee
A blinded Clinical Event Committee will adjudicate potential MACE (cardiovascular death, 
myocardial infarction, stroke), other cardiovascular events (such as hospitalization for unstable 
angina, hospitalization for heart failure, serious arrhythmia, resuscitated sudden death, 
cardiogenic shock, coronary revascularization [eg, coronary artery bypass graft or percutaneous 
coronary intervention]), venous and arterial thrombotic events, and noncardiovascular deaths.  

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Details of membership, operations, recommendations from the Committee, and the 
communication plan will be documented in the Charter.

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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
AA
alopecia areata
AA-IGA
Alopecia Areata Investigator Global Assessment
AD
atopic dermatitis
AE
adverse event:  any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can, therefore, be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANCOVA
analysis of covariance
APC
activated protein C
APTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AT
alopecia areata totalis
ATE
arterial thrombotic event
AU
alopecia areata universalis
BCG
Bacillus Calmette-Guérin vaccine
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the Sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
A double-blind study is one in which neither the patient nor any of the investigator or 
Sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received.
BMI
body mass index
BUN
blood urea nitrogen
CI
confidence interval

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CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
ClinRO
clinician-reported outcome
CPK
creatinine phosphokinase
CRF
case report form
CRP
clinical research physician
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DVT
deep vein thrombosis
ECG
electrocardiogram
eCOA
electronic clinical outcome assessment
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
ePRO/PRO
electronic patient-reported outcome/patient-reported outcome
EQ-5D-5L
European Quality of Life – 5 Dimensions – 5 Level
ERB
ethical review board
ET
early termination 
FAS
full analysis set
FDA
Food and Drug Administration
F-DBL
final database lock
FSH
follicle-stimulating hormone
fXa
clotting factor Xa
GBD
Global Burden of Disease 
GCP
good clinical practice
GGT
gamma-glutamyltransferase

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GPS
Global Patient Safety
HADS
Hospital Anxiety and Depression Scale
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IAS
interim analysis set
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IFNγ
interferon gamma
Ig
immunoglobulin
IL
interleukin
INR
international normalized ratio
IP
investigational product:  a pharmaceutical form of an active ingredient or placebo being 
tested or used as a reference in a clinical trial, including products already on the market 
when used or assembled (formulated or packaged) in a way different from the 
authorized form, or marketed products used for an unauthorized indication, or marketed 
products used to gain further information about the authorized form.
IRB
institutional review board
IV
intravenous
IWRS
interactive web-response system
JAK
Janus kinase
LS
least squares 
MACE
major adverse cardiovascular events
MCMC
Markov chain Monte Carlo method
MCS
mental component score

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MedDRA
Medical Dictionary for Regulatory Activities
MHC
major histocompatibility complex
mFAS
modified full analysis set
MI
multiple imputation
mLOCF
modified last observation carried forward
MMRM
mixed-effects model of repeated measures
mRNA
messenger RNA
MTHFR
methylene tetrahydrofolate reductase
NRI
nonresponder imputation
PCS
physical component score
PD
pharmacodynamics(s)
PE
pulmonary embolism
PK
pharmacokinetic(s)
pMI
placebo multiple imputation
PO-DBL
primary outcome database lock
PPD
purified protein derivative
PPS
per-protocol set
PRO/ePRO
patient-reported outcome/electronic patient-reported outcome
PT
prothrombin time
PTT
partial thromboplastin time
QD
once daily administration
RA
rheumatoid arthritis
RBC
red blood cell
RNA
ribonucleic acid
SAE
serious adverse event
SALT
Severity of Alopecia Tool
SALT30
at least 30% improvement from Baseline in SALT score

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SALT50
at least 50% improvement from Baseline in SALT score
SALT75
at least 75% improvement from Baseline in SALT score
SALT90
at least 90% improvement from Baseline in SALT score
SAP
statistical analysis plan
SF-36
Short-Form Health Survey
SOA
Schedule of Events
STAT
signal transducer and activator of transcription
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBL
total bilirubin level
TEAE
treatment-emergent adverse event:  an untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, which does not necessarily have to have a causal relationship 
with this treatment.
TSH
thyroid-stimulating hormone
TYK2
tyrosine kinase 2
ULN
upper limit of normal
VAS
Visual Analog Scale
VTE
venous thromboembolic event
WBC
white blood cell

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Appendix 2. Clinical Laboratory Tests
Hematologya,b
Clinical Chemistrya,b
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Absolute Reticulocyte Count
Total bilirubin
Mean cell volume
Direct bilirubin
Mean cell hemoglobin
Alkaline phosphatase
Mean cell hemoglobin concentration
Alanine aminotransferase (ALT)
Leukocytes (WBC)
Aspartate aminotransferase (AST)
Platelets
Blood urea nitrogen (BUN)
Absolute counts of:
Creatinine
Neutrophils, segmented
Cystatin C
Neutrophils, juvenile (bands)
Uric acid
Lymphocytes
Calcium
Monocytes
Glucose
Eosinophils
Albumin
Basophils
Total protein
Estimated glomerular filtration rate (eGFR)e
Creatine phosphokinase (CPK)
Urinalysisa,b,d
Color
Other Testsa
Specific gravity
Hepatitis B Surface antigen (HBsAg)f
pH
Anti-Hepatitis B Core antibody (HBcAb)f
Protein
Hepatitis B virus (HBV) DNAl
Glucose
Anti-Hepatitis B Surface antibody (HBsAb)f
Ketones
Human immunodeficiency virus (HIV)f
Bilirubin
Hepatitis C antibodyf,g
Urobilinogen
Thyroid-stimulating hormone (TSH)f
Blood
Exploratory storage samples (serum, plasma and mRNA)
Leukocyte esterase
Pregnancy Testh
Nitrite
Follicle-stimulating hormonef,i
QuantiFERON-TB Goldj (central testing preferred) or 
T-SPOT.TB k (local testing)
Lipidsa,c
PPD (local testing/reading)
Total cholesterol
Baricitinib plasma levels
Low-density lipoprotein
Serum immunoglobulin (IgE)
High-density lipoprotein
Triglycerides
Abbreviations:  DNA = deoxyribonucleic acid; mRNA = messenger ribonucleic acid; FSH = follicle-stimulating 
hormone; HBV = hepatitis B virus; IgE = immunoglobulin E; PPD = purified protein derivative; RBC = red 
blood cell; TB = tuberculosis; WBC = white blood cell.
a
Assayed by Sponsor-designated laboratory.
b
Unscheduled or repeat blood chemistry, hematology, and urinalysis panels may be performed at the discretion of 
the investigator, as needed.

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c
Fasting lipid profile.  Patients should not eat or drink anything except water for 8 hours prior to test.  If a patient 
attends these visits in a nonfasting state, this will not be considered a protocol violation.
d
Microscopic examination of sediment performed only if abnormalities are noted on the routine urinalysis.
e
Estimated glomerular filtration rate for serum creatinine calculated by the central laboratory using the Chronic 
Kidney Disease Epidemiology Collaboration creatinine 2009 equation.
f
Test required at Visit 1 only to determine eligibility of patient for the study.
g
A positive hepatitis C antibody result will be confirmed with an alternate hepatitis C method.
h
For all women of childbearing potential, a serum pregnancy test will be performed at Visit 1 and a local urine 
pregnancy test will be performed at Visit 2 and at all subsequent study visits.  If required per local regulations 
and/or institutional guidelines, pregnancy testing can occur at other times during the study treatment period.
i
To confirm postmenopausal status for women ≥40 and <60 years of age who have had a cessation of menses, an 
FSH test will be performed.  Nonchildbearing potential is defined as an FSH ≥40 mIU/mL and a cessation of 
menses for at least 12 months.
j
The QuantiFERON-TB Gold test (central testing) is the preferred alternative to the PPD test for the evaluation of 
TB infection, and it may be used instead of the PPD test or T-SPOT.TB test.  If the QuantiFERON-TB Gold test 
is indeterminate, 1 retest is allowed.  
k
T-SPOT.TB must be read locally.  
l
HBV DNA testing will be done in those patients who are HBcAb+ at screening, regardless of HBsAb status.

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Appendix 3.
Study Governance Considerations

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

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Appendix 3.1.4. Regulatory Considerations
This study will be conducted in accordance with the protocol and with the:

consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the Sponsor will be assigned to a third party.
Appendix 3.1.5. Investigator Information
Physicians with expertise in the diagnosis and treatment of alopecia areata will participate as 
investigators in this clinical trial.
Appendix 3.1.6. Protocol Signatures
The Sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his/her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.7. Final Report Signature
Lilly will select a qualified investigator(s) from among investigators participating in the design, 
conduct, and/or analysis of the study to serve as the clinical study report (CSR) coordinating 
investigator.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the CSR coordinating investigator.
The CSR coordinating investigator will sign the final CSR for this study, indicating agreement 
that, to the best of his/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/her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 3.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate.

sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the case report forms 
(CRFs), and study procedures.

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
make periodic visits to the study site.

be available for consultation and stay in contact with the study site personnel by mail, 
telephone, and/or fax.

review and evaluate CRF data and use standard computer edits to detect errors in data 
collection.

conduct a quality review of the database.
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the Sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1. Data Capture System
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site into the Sponsor-provided electronic data capture system.
Electronic patient-reported outcome (ePRO) measures (eg, a rating scale) and electronic clinical 
outcome assessments (eCOAs) are entered into an ePRO/eCOA instrument at the time that the 
information is obtained.  In those instances where there is no prior written or electronic source 
data at the site, the ePRO/eCOA instrument record will serve as the source.
If ePRO/eCOA records are stored at a third-party site, investigator sites will have continuous 
access to the source documents during the study and will receive an archival copy at the end of 
the study for retention.
Any data for which the ePRO/eCOA instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file.
Case report form data will be encoded and stored in InForm.  
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

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Appendix 3.3.
Study and Site Closure
Appendix 3.3.1. Discontinuation of Study Sites
Study site participation may be discontinued if Lilly, the investigator, or the ERB of the study 
site judges it necessary for medical, safety, regulatory, or other reasons consistent with 
applicable laws, regulations, and GCP.
Appendix 3.3.2. Discontinuation of the Study
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP.  Study termination may 
occur in a specific country or region when baricitinib is approved for the treatment of AA and 
becomes reimbursed or commercially available in that country or region, or a negative regulatory 
action or opinion is received in that country or region.
Appendix 3.4.
Publication Policy
The publication policy for Study I4V-MC-JAHO is described in the Clinical Trial Agreement.

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

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Appendix 5.
Liver Function Testing and Hepatic Safety 
Monitoring
Liver Function Testing and Hepatic Safety Monitoring
Analyte
Exclusion
Criteria
Additional 
Hepatic 
Testing
Hepatic eCRF 
Reporting
Temporary 
Interruption of 
IP
Permanent Discontinuation 
of IP after Consultation 
with the Lilly-Designated 
Medical Monitor
Protocol 
Section
Section 6.2
Section 9.4.10.1
Section 9.4.10.1
Section 8.1.1
Section 8.1.1
ALT/AST
≥2 × ULN
As per protocol 
only ALT 
>3 × ULN
As per protocol 
only ALT 
≥5 × ULN on 
≥2 consecutive 
tests
≥5 × ULN

>8 × ULN

>5 × ULN for >2 weeks

>3 × ULN AND TBL 
>2 × ULN or INR >1.5

>3 × ULN with 
symptomsa
ALP
≥2 × ULN
≥2 × ULN
≥2 × ULN on 
≥2 consecutive 
tests
No applicable 
criteria

>3 × ULN

>2.5 × ULN AND TBL 
>2 × ULN 

>2.5 × ULN with 
symptomsa
TBL
≥1.5 × ULN
≥2 × ULN
≥2 × ULN
(excluding 
Gilbert’s 
syndrome)
No applicable 
criteria

ALT or AST (as per 
protocol) >3 × ULN 
AND TBL >2 × ULN

ALP >2.5 × ULN AND
TBL >2 × ULN
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
eCRF = electronic case report form; 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, rash, and/or eosinophilia (>5%).

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Appendix 6.
Additional Information on Statistical 
Methods
Appendix 6.1. Statistical Methods for Additional Analyses
Appendix 6.1.1. Placebo Multiple Imputation
The placebo multiple imputation (pMI) method may be used as an additional analysis for the 
analysis of the primary efficacy endpoint, as well as key secondary endpoints.  Multiple 
imputations are used to replace missing outcomes (defined in SAP) (Severity of Alopecia Tool 
[SALT] score, patient-reported outcome [PRO] for Scalp Hair Assessment score, etc.) for drug-
and placebo-treated patients using multiple draws from the posterior predictive distribution 
estimated from the placebo arm.  The binary outcomes (SALT ≤20, PRO for Scalp Hair 
Assessment score of 0 or 1 with a ≥2-point improvement, etc.) will be derived from the imputed 
data.
Data are processed sequentially by repeatedly calling SAS® PROC MI to impute missing 
outcomes at visits t=1,.., T.
1. Initialization:  Set t=0 (Baseline visit)
2. Iteration:  Set t=t+1. Create a data set combining records from drug- and 
placebo-treated patients with columns for covariates X and outcomes at visits 1,..,t
with outcomes for all drug-treated patients set to missing at visit t and set to observed 
or imputed values at visits 1,..,t-1.
3. Imputation:  Run Bayesian regression in SAS® PROC MI on this data to impute 
missing values for visit t using previous outcomes for visits 1 to t-1 and baseline 
covariates. Note that only placebo data will be used to estimate the imputation model 
because no outcome is available for drug-treated patients at visit t.
4. Replace imputed data for all drug-treated patients at visit t with their observed values, 
whenever available up to permanent study drug discontinuation or study 
discontinuation. If t < T, then go to Step 2, otherwise proceed to Step 5.
5. Repeat steps 1-4, m times with different seed values to create m imputed complete 
data sets.
Note that a Markov chain Monte Carlo method will be used to create a monotone missing pattern
first in the presence of intermittent missing data.
Analysis For the primary and key secondary efficacy endpoints, the missing outcomes will be 
derived from the imputed data for each patient before fitting into the analysis model.  A logistic 
regression or analysis of covariance (ANCOVA)will be applied, as appropriate.  
The number of imputed data sets will be m=100 and a 6-digit seed value will be pre-specified for 
each analysis.  Within the program, the seed will be used to generate the m seeds needed for 
imputation. The initial seed values are given below:  

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Analysis 
Seed Value
Proportion of patients achieving SALT ≤20 at Weeks 16, 24, and 36
123450
Proportion of patients achieving a PRO for Scalp Hair Assessment 0 or 1 with a ≥2-point 
improvement from Baseline at Week 36 among patients with a score of ≥3 at Baseline
123451
Proportion of patients achieving an absolute SALT score ≤ 10 at Weeks 24 and 36
123450
Proportion of patients achieving SALT90 at Week 36
123450
Proportion of patients achieving SALT50 at Week 12
123450
Percent change from Baseline in SALT score at Week 36
123450
Proportion of patients achieving ClinRO Measure for EB Hair Loss 0 or 1 with ≥2-point 
improvement from Baseline at Week 36 (among patients with ClinRO Measure for EB Hair 
Loss ≥2 at Baseline)
123452
Proportion of patients achieving ClinRO Measure for EL Hair Loss 0 or 1 with ≥2-point 
improvement from Baseline at Week36 (among patients with ClinRO Measure for EL Hair 
Loss ≥2 at Baseline)
123453
Abbreviations:  ClinRO = clinician-reported outcome; EB = eyebrow; EL = eyelash; PRO = patient-reported 
outcome; SALT = Severity of Alopecia Tool; SALT50 = at least 50% improvement from Baseline in SALT 
score; SALT90 = at least 90% improvement from Baseline in SALT score.
The final inference on treatment difference is conducted from the multiple data sets using 
Rubin’s combining rules, as implemented in SAS® PROC MIANALYZE. 
Thus, in the effectiveness context, pMI assumes no pharmacological benefit of the drug after 
dropout.  It limits bias by taking into account study/placebo effects. In the efficacy context, pMI 
is a specific form of a missing not at random analysis expected to yield a conservative estimate 
of efficacy. 
Appendix 6.1.2. Tipping Point Analyses
To investigate the missing data mechanism, an additional analysis using multiple imputation 
(MI) under the missing not at random assumption may be provided for the primary objective, 
which compares the SALT ≤20 response rate of each of the baricitinib 4-mg and 2-mg doses to
placebo at Week 36.  The tipping point analysis may also be used as an additional sensitivity 
analysis for some key secondary objectives.
All patients in the full analysis set (FAS) population are included.  Within each analysis, the 
most extreme case will be considered, in which all missing data (defined in SAP) for patients 
randomized to the baricitinib doses will be imputed using the worst possible result, and all 
missing data (defined in SAP) for patients randomized to placebo will be imputed with the best 
possible result.  Treatment differences will be analyzed using logistic regression or analysis of 
covariance (ANCOVA), as appropriate.  

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For continuous variables, the following process will be used to determine the tipping point:
1. To handle intermittent missing visit data, a Markov chain Monte Carlo method 
(SAS® Proc MI with MCMC option) will be used to create a monotone missing 
pattern. 
2. A set of Bayesian regressions (using SAS® Proc MI with MONOTONE option) will 
be used for the imputation of monotone dropouts.  Starting from the first visit with at 
least 1 missing value, the regression models will be fit sequentially with treatment as 
a fixed effect and values from the previous visits as covariates.  
3. A delta score is added to all imputed scores at the timepoint where the analysis is 
conducted for patients in the baricitinib treatment groups, thus, worsening the 
imputed value.  The delta score is capped for patients, based on the range of the 
outcome measure being analyzed.
4. Treatment differences between baricitinib and placebo are analyzed for each imputed 
data set using ANCOVA.  Results across the imputed data sets are aggregated using 
SAS® Proc MIANALYZE in order to compute a p-value for the treatment 
comparisons for the given delta value.
5. Steps 3 and 4 are repeated, and the delta value added to the imputed baricitinib scores 
is gradually increased.  The tipping point is identified as the delta value which leads 
to a loss of statistical significance (aggregated p-value >0.05) when evaluating 
baricitinib relative to the placebo group.
As a reference, for each delta value used in Steps 3-5, a fixed selection of delta values (ranging 
from slightly negative to slightly positive) will be added to imputed values in the placebo group, 
and Step 4 will be performed for the combination.  This will result in a 2-d table for each 
timepoint of interest, with the columns representing the delta values added to the imputed 
placebo responses, and the rows representing the delta values added to the imputed baricitinib 
responses.  Separate 2-d tables will compare each baricitinib dose group to placebo.
A similar process will be used for the categorical variables:
1. Missing responses in the baricitinib groups will be imputed with a range of low response 
probabilities, including probabilities of 0, 0.1, and 0.2.
2. For missing responses in the placebo group, a range of response probabilities 
(eg, probability = 0, 0.2, … 1) will be used to impute the missing values.  Multiple 
imputed data sets will be generated for each response probability.
3. Treatment differences between baricitinib and placebo are analyzed for each imputed 
data set using logistic regression.  Results across the imputed data sets are aggregated 
using SAS® Proc MIANALYZE in order to compute a p-value for the treatment 
comparisons for the given response probability.  If the probability values do not allow for 
any variation between the multiple imputed data sets (eg, all missing responses in the 

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placebo and baricitinib groups are imputed as responders and nonresponders, 
respectively), then the p-value from the single imputed data set will be used.
The tipping point is identified as the response probability value within the placebo group that 
leads to a loss of statistical significance when evaluating baricitinib relative to placebo. 
For tipping point analyses the number of imputed data sets will be m=100 and the seed value to 
start the pseudorandom number generator of SAS Proc MI (same values for MCMC option and 
for MONOTONE option) will be: 
Analysis
Seed value
Proportion of patients achieving SALT ≤20 at Week 36
123461
Appendix 6.2.
Graphical Testing Procedures
The primary hypotheses H1,1,0 and H2,1,0 will be first tested at a two-sided α=0.04 and 0.01, 
respectively. If neither of the null hypotheses is  rejected, no further testing is conducted, as the 
α for that test is considered “spent” and cannot be passed to other endpoints. If at least one of the 
null hypotheses is rejected, the testing process continues, with the remaining α propagated 
according to the weights on the corresponding edges displayed in (Figure JAHO.3).  The testing 
process continues as long as there is at least one hypothesis in the scheme that can be rejected at 
its allocated α level at that point.  Each time a hypothesis is rejected, the graph is updated to 
reflect the reallocation of α, which is considered “recycled” by Alosh et al. (2014).  This iterative 
process of updating the graph and reallocating α is repeated until all hypotheses have been tested 
or when no remaining hypotheses can be rejected at their corresponding α levels.
There will be no adjustment for multiple comparisons for any other analyses. 

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

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Appendix 8.
Provisions for Changes in Study Conduct 
During Exceptional Circumstances
Implementation of this appendix
The changes to procedures described in this appendix are temporary measures intended to be 
used only during specific time periods as directed by the sponsor in partnership with the 
investigator.
Exceptional circumstances
Exceptional circumstances are rare events that may cause disruptions to the conduct of the study.
Examples include pandemics or natural disasters.  These disruptions may limit the ability of the 
investigators, participants, or both to attend on-site visits or to conduct planned study procedures.
Implementing changes under exceptional circumstances
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may 
implement changes if permitted by local regulations. 
After approval by local ERBs, regulatory bodies and any other relevant local authorities, 
implementation of these exceptional circumstances changes will not typically require additional 
notification to these groups, unless they have specific conditions in which notification is required. 
To protect the safety of study participants, urgent changes may be implemented before approval 
but need to be reported as soon as possible. All approvals must be retained in the study records.
In the event written approval is granted by the sponsor for changes in study conduct, additional 
written guidance, if needed, will be provided by the sponsor.
Considerations for making a change
The prevailing consideration for making a change is ensuring the safety of study participants.
Additional important considerations for making a change are compliance with Good Clinical 
Practice, enabling participants to continue safely in the study and maintaining the integrity of the 
study. 
Informed Consent
The site should document the participant’s verbal consent for having remote visits and remote 
dispensing of IP, ancillaries, prior to implementation of these activities.
Additional consent from the participant will be obtained, if required, for:

participation in remote visits, as defined in Section “Remote Visits,”

a change in the method, location, or both, of study intervention administration,

dispensation of additional study intervention during an extended treatment period, 

alternate delivery of study intervention and ancillary supplies, and

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
provision of their personal or medical information required prior to implementation of 
these activities. 
Changes in Study Conduct During Exceptional circumstances
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed.
The following changes in study conduct will not be considered protocol deviations.
1. Remote visits
Visit 8 (Week 36) requires a live clinical assessment because it is the primary outcome 
visit. To facilitate an onsite visit, the visit window may be extended (see below in
Adjustment to Visit Windows of this appendix).
All other visits (including assessment of loss of benefit during randomized down 
titration post Week 52), may be conducted remotely if the visit could not otherwise be 
conducted due to local or national restrictions.
In source documents and the CRF, the study site should capture the visit location and method,
with a specific explanation for any data missing because of missed in-person site visits.
Telemedicine: Live, onsite clinical efficacy assessments are preferred for ALL visits; however, 
if a remote visit is the only option, telephone or technology-assisted virtual visits, or both, are 
acceptable to complete appropriate assessments (with the exception of Visit 8).  Assessments to 
be completed in this manner include:

PRO Scalp, SALT Score, and ClinROs for Eyebrows/Eyelashes if Visual 
Assessment by telemedicine is possible. If NO visual assessment AND ONLY 
verbal assessment by phone is possible. SALT, ClinROs for Eyelash/Eyelash, 
Nails, PROs for Eye Irritation should not be assessed. 

AEs and product complaints

concomitant medications

C-SSRS (Since Last Visit Version), Self-Harm Supplement Form, and Self-Harm

Photos should be captured at next onsite visit after a remote V8 or V11/ET
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of adverse events (AEs), serious adverse events (SAEs), and product complaints 
remain unchanged. Furthermore, every effort should be made to enable participants to return to 
on-site visits as soon as reasonably possible, while ensuring the safety of both the participants
and the site staff.
2. Local laboratory testing option
Local laboratory testing may be conducted in lieu of central laboratory testing. The local 
laboratory must be qualified in accordance with applicable local regulations.

Obtain local labs for safety (hematology, chemistry) and urine pregnancy when 
applicable, as per the study protocol schedule of activities.

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
A urine pregnancy test should be sent to female patients of child bearing potential.  
The patient should conduct the test and provide verification of results to the site per a 
method agreed to between the patient and the site. Investigational product must be 
temporarily held until site can review photo of pregnancy test results.

All labs will be reviewed by the investigators. Lilly Medical should be informed of 
any labs that meet criteria for temporary or permanent study drug discontinuation.

Sign and date review of local labs per normal process and follow-up with the patient 
as needed. Results will not be recorded in the eCRF.

Safety labs should be obtained at a minimum of every 12 weeks and IP should not be 
dispensed until these can be collected and reviewed.
3. Study intervention and ancillary supplies 
When a participant is unable to go to the site to receive study supplies during normal on-site 
visits, the site should work with the sponsor to determine appropriate actions.  These actions 
may include: 

asking the participant to go to the site and receive study supplies from site staff 
without completion of a full study visit, 

asking the participant’s designee to go to the site and receive study supplies on a 
participant’s behalf, 

arranging delivery of study supplies.
These requirements must be met before action is taken:

Sponsor approves the alternative method of delivery, taking local regulatory 
requirements into consideration.

Participant consents verbally to alternate method of delivery.

Site confirms the participant’s receipt of the trial supplies.

Site/sponsor confirms appropriate ethics review board notification.

Alternate delivery of IP should be performed in a manner that does not compromise 
treatment blinding and ensures product integrity. The existing protocol requirements 
for product accountability remain unchanged, including verification of participant’s 
receipt of study supplies.

When delivering supplies to a location other than the study site (for example, 
participant’s home), the investigator, sponsor, or both should ensure oversight of the 
shipping process to ensure accountability and product quality (that is, storage 
conditions maintained and intact packaging upon receipt).

Instructions may be provided to the participant or designee on the final disposition of 
any unused or completed study supplies.
4. Screening period guidance 
Not Applicable 
5. Adjustments to Visit Windows 

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Whenever possible and safe to do so, as determined by the investigator’s discretion, 
participants should complete the usual Schedule of Activities. To maximize the possibility 
that these visits can be conducted as on-site visits, the windows for visits may be adjusted, 
upon further guidance from the sponsor. This minimizes missing data and preserves the 
intended conduct of the study.
This table describes the allowed adjustments to visit windows.
Visit Number
Tolerance
Visits 8
Visits 8 (Week 36) may be conducted within 7 days before 
the intended date, or up to 28 days after the intended date
All other Visits
All other visits should be conducted as per the visit window 
the stated in the Schedule of Activities in Section 2
Documentation
Changes to study conduct will be documented:

Sites will identify and document the details of how participants, visit types, and 
conducted activities were affected by exceptional circumstances. 
Dispensing/shipment records of study intervention and relevant communications, 
including delegation, should be filed with site study records.

Source documents generated at a location other than the study site should be part of 
the investigator’s source documentation and should be transferred to the site in a 
secure and timely manner. 

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Appendix 9.
Protocol Amendment I4V-MC-JAHO(e)
Summary
Overview
Protocol I4V-MC-JAHO A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 
Operationally Seamless, Adaptive Phase 2/3 Study to Evaluate the Efficacy and Safety of 
Baricitinib in Adult Patients with Severe or Very Severe Alopecia Areata (BRAVE-AA1) has 
been amended.  The new protocol is indicated by amendment (e) and will be used to conduct the 
study in place of any preceding version of the protocol.
This protocol has been amended to:

finalize key secondary endpoints prior to primary outcome database lock, 

update and clarify statistical analysis, 

modify graphical testing to align with the updates to key secondary endpoints, 

add Appendix 8 to allow for remote visits in the event of extraordinary events, and

correct typographical errors, clarify study procedures, and increase flexibility of overall 
study.  
The overall changes and rationale for the changes made to this protocol are described in the 
following table.

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Amendment Summary for Protocol I4V-MC-JAHO Amendment (e)
Section # and Name
Description of Change
Brief Rationale
Section 1. Synopsis

Added proportion of patients achieving SALT50 at Week 12 to Key 
Secondary Objectives

Moved Week 24 timepoint for Proportion of patient achieving a SALT90
to Other Secondary Endpoints

Changed timepoint for percent change from baseline in SALT score to
Week 36 and moved Week 12 to Other Secondary Endpoints

Moved proportion of patients achieving SALT50 at Week 12 from Other 
Secondary Endpoints to Key Secondary Endpoints

Moved ClinROs for EB and EL to Key Secondary Endpoints at Week 36 
from Other Secondary Endpoints

Moved Proportion of patients achieving ClinRO Measure for EB Hair 
Loss 0 or 1 with ≥2-point improvement from baseline at Week 36 (among 
patients with ClinRO Measure for EB Hair Loss ≥2 at Baseline) from 
Other Secondary Endpoints to Key Secondary Endpoints

Moved Weeks 16 and 24 for Proportion of patients with PRO for Scalp 
Hair Assessment score of 0 or 1 to Other Secondary Endpoints

Clarified ClinRO and PRO endpoints

Change from Baseline in SALT score at Weeks 12, 16, 24, and 36 added 
to Other Secondary

Added clarifying statement in regard to the potential for additional 
database locks and Interim Analysis

Clarified Mean change from Baseline in HADS total score at Weeks 24 
and 36 to specify HADS-A and HADS-D

Changed 95% CI will be reported, to may be reported 

Removed Baseline testing for Fisher exact test

Updated key 
secondary 
endpoints to 
reflect the 
analysis that 
will be 
conducted

For flexibility

Error
Section 2. SoA
Added leading statement regarding addition of Appendix 8 which addresses 
provisions in study conduct under exceptional circumstances
For clarity on 
addition of 
Appendix 8
Section 4. Objectives and Endpoints

Added proportion of patients achieving SALT50 at Week 12 to Key 
Secondary Objectives

Moved Week 24 timepoint for Proportion of patients achieving a SALT90
to Other Secondary Endpoints

Changed timepoint for percent change from baseline in SALT score to 
Week 36 and moved Week 12 to Other Secondary Endpoints

Updated key 
secondary 
endpoints to 
reflect the 
analysis that 
will be 

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
Moved proportion of patients achieving SALT50 at Week 12 from Other 
Secondary Endpoints to Key Secondary Endpoints

Moved ClinROs for EB and EL to Key Secondary Endpoints at Week 36 
from Other Secondary Endpoints

Moved Proportion of patients achieving ClinRO Measure for EB Hair 
Loss 0 or 1 with ≥2-point improvement from baseline at Week 36 (among 
patients with ClinRO Measure for EB Hair Loss ≥2 at Baseline) from 
Other Secondary Endpoints to Key Secondary Endpoints

Moved Weeks 16 and 24 for Proportion of patients with PRO for Scalp 
Hair Assessment score of 0 or 1 to Other Secondary Endpoints

Clarified ClinRO and PRO endpoints

Change from Baseline in SALT score at Weeks 12, 16, 24, and 36 added 
to Other Secondary

Added clarifying statement in regard to the potential for additional 
database locks and Interim Analysis

Clarified Mean change from Baseline in HADS total score at Weeks 24 
and 36 to specify HADS-A and HADs-D

Added EQ-5D-5L and SF-36 abbreviations
conducted
Section 5.1.1. Stage 1 (Includes Phase 2 Portion 
and Phase 3 Portion before Decision Point)
Section 5.1.3. Stage 2 (Remaining Portion of 
Phase 3 Study after the Decision Point)

Removed wording referring to AA severity to improve clarity of 
stratification

For clarity 
based on 
regulatory 
feedback
Section 6.1. Inclusion Criteria

Updated pregnancy language

For Clarity 
Section 7.2. Method of Treatment Assignment 

Removed wording referring to AA severity to improve clarity of 
stratification

Visit and Week information corrected

Regulatory 
feedback

Error
Section 9.4.4. Laboratory Tests

Clarified blood and urine collection for home visits are permitted under 
normal protocol operations

For flexibility 
in study 
conduct 
Section 10.3.1. General Statistical 
Considerations

Sentence added to allow for additional database locks and interim 
analyses being conducted

For flexibility 
and to support 
scientific 
disclosures
Section 10.3.1.1. Analysis Methods

95% CI will also be reported changed to may be reported

Error

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Section 10.3.1.2. Missing Data Imputation

Statements removed to clarify sensitivity analysis may be conducted

The specification for additional analysis was updated

pMI analysis was changed from will be included to may be included

For flexibility 
Section 10.3.1.3. Multiple 
Comparisons/Multiplicity

Update Graphical testing procedures to reflect planned analysis (Figure 
JAHO.3)

Key Secondaries Null Hypotheses Updated to reflect updates to Key 
Secondary Objectives

Updated based 
on revision to 
Key Secondary 
Endpoints
Section 10.3.3.1. Primary Analyses

Statement updated to clarify that additional analysis of the primary 
efficacy outcome may be performed

Updated based 
on Regulatory 
feedback
Section 10.3.3.2. Secondary Analyses

Statement updated to clarify that additional analysis of the secondary 
efficacy outcome may be performed 

Updated based 
on Regulatory 
feedback
Section 10.3.4. Safety Analyses

Updated wording to clarify data included in the safety analysis

For clarity 
Section 10.3.6.1. Subgroup Analyses

Added baseline value wording to logistic model

For clarity 
Section 10.3.7.3.2. Week 36 Primary Outcome 
Analysis and Other Regulatory Submission 
Activities 

Updated 4 month safety update database lock to 3 to 4 month safety 
update data base lock

Added additional efficacy/safety interim analyses are also done to support 
scientific disclosures.

For flexibility 
Appendix 6.1.1. Placebo Multiple Imputation

Sentence added in stating that a Markov chain Monte Carlo method will 
be used

Analysis table adjusted to reflect planned analysis and updated objectives

Removed statement about mLOCF

For clarity 
Appendix 8 Provisions for Changes in Study 
Conduct During Exceptional Circumstances

Added Provisions for Changes in Study Conduct During Exceptional 
Circumstances Appendix 

Allows for 
continued 
conduct of the 
study using 
remote visits
and increases 
flexibility
Abbreviations: AA = alopecia areata; CI = Confidence Interval; ClinRO = clinician-reported outcome; EB = eyebrow; EL = eyelash; EQ-5D-5L= European 
Quality of Life – 5 Dimensions – 5 Level; mLOCF = modified last observation carried forward; pMI = placebo multiple imputation; PRO = patient-reported 
outcome; SALT = Severity of Alopecia Tool; SALT50 = at least 50% improvement from Baseline in Severity of Alopecia Tool score; SALT90 = at least 90% 
improvement from Baseline in Severity of Alopecia Tool score; SF-36 = Short Form-36 Health Survey acute version 2.

Leo Document ID = fa08c39c-2a1c-4e5f-9d93-23441e9d7e8f
Approver: 
Approval Date & Time: 02-Nov-2020 19:28:21 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 02-Nov-2020 20:59:54 GMT
Signature meaning: Approved
PPD
PPD