A Multicenter, Randomized, Double-Blind, Placebo- Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients With Severe or Very Severe Alopecia Areata
Phase: PHASE3
Conditions: Alopecia Areata
Sponsor: Eli Lilly and Company

I4V-MC-JAIR Protocol (d) 
 
A Multicenter, Randomized, Double-Blind, Placebo Controlled, Phase 3 Study to Evaluate the 
Efficacy and Safety of Baricitinib in Adult Patients with Severe or Very Severe Alopecia Areata 
 
NCT03899259 
 
Approval Date: 02-Nov-2020 

I4V-MC-JAIR(d) Clinical Protocol
Page 1
LY3009104
Protocol I4V-MC-JAIR(d)
A Multicenter, Randomized, Double-Blind, Placebo-
Controlled, Phase 3 Study to Evaluate the Efficacy and 
Safety of Baricitinib in Adult Patients with Severe or Very 
Severe Alopecia Areata
BRAVE-AA2
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 26 October 2018.
Amendment (a) Electronically Signed and Approved by Lilly on 09-Nov-2018
Amendment (b) Electronically Signed and Approved by Lilly 05-Oct-2019
Amendment (c) Electronically Signed and Approved by Lilly 01-Jun-2020
Amendment (d) Electronically Signed and Approved by Lilly
on date provided below.
Approval Date: 02-Nov-2020 GMT

I4V-MC-JAIR(d) Clinical Protocol
Page 2
LY3009104
Table of Contents
Section
Page
Protocol I4V-MC-JAIR(d) A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and 
Safety of Baricitinib in Adult Patients with Severe or Very Severe 
Alopecia Areata  BRAVE-AA2...........................................................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................17
3.
Introduction ......................................................................................................................24
3.1.
Study Rationale............................................................................................................24
3.2.
Background..................................................................................................................25
3.3.
Benefit/Risk Assessment..............................................................................................26
4.
Objectives and Endpoints..................................................................................................29
5.
Study Design.....................................................................................................................32
5.1.
Overall Design .............................................................................................................32
5.1.1.
Period 1:  Screening (-35 to -3 days) ....................................................................35
5.1.2.
Period 2:  Double-Blind Treatment Period (Weeks 0 – 36)...................................35
5.1.3.
Period 3:  Long-Term Extension ..........................................................................35
5.1.4.
Period 4:  Bridging Extension...............................................................................37
5.1.5.
Period 5:  Posttreatment Follow-Up......................................................................37
5.2.
Number of Participants.................................................................................................38
5.3.
End of Study Definition ...............................................................................................38
5.4.
Scientific Rationale for Study Design...........................................................................38
5.5.
Justification for Dose ...................................................................................................39
5.5.1.
Rationale for Dose Adjustment for Renal Impairment ..........................................40
6.
Study Population...............................................................................................................41
6.1.
Inclusion Criteria..........................................................................................................41
6.2.
Exclusion Criteria ........................................................................................................43
6.3.
Lifestyle Restrictions....................................................................................................50
6.4.
Screen Failures.............................................................................................................50
7.
Treatments........................................................................................................................51
7.1.
Treatments Administered .............................................................................................51
7.1.1.
Packaging and Labeling .......................................................................................51
7.2.
Method of Treatment Assignment ................................................................................51
7.2.1.
Selection and Timing of Doses.............................................................................52

I4V-MC-JAIR(d) Clinical Protocol
Page 3
LY3009104
7.2.2.
Dose Adjustment for Renal Impairment ...............................................................52
7.3.
Blinding .......................................................................................................................52
7.4.
Dosage Modification....................................................................................................53
7.5.
Preparation/Handling/Storage/Accountability...............................................................53
7.6.
Treatment Compliance .................................................................................................53
7.7.
Concomitant Therapy...................................................................................................54
7.7.1.
Permitted Medications and Procedures.................................................................54
7.7.2.
Prohibited Medications and Procedures................................................................54
7.8.
Treatment after the End of the Study............................................................................55
7.8.1.
Continued Access.................................................................................................55
8.
Discontinuation Criteria ....................................................................................................57
8.1.
Discontinuation from Study Treatment.........................................................................57
8.1.1.
Permanent Discontinuation from Study Treatment ...............................................57
8.1.2.
Temporary Interruption of Investigational Product ...............................................58
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................60
8.2.
Discontinuation from the Study....................................................................................60
8.3.
Lost to Follow-Up........................................................................................................61
9.
Study Assessments and Procedures ...................................................................................62
9.1.
Efficacy Assessments...................................................................................................62
9.1.1.
Primary Efficacy Assessments .............................................................................62
9.1.1.1.
Severity of Alopecia Tool (SALT) Score........................................................62
9.1.2.
Secondary Efficacy Assessments..........................................................................62
9.1.2.1.
Alopecia Areata Patient-Reported Outcomes ..................................................62
9.1.2.1.1.
Scalp Hair Assessment PRO™.................................................................62
9.1.2.1.2.
Other Patient Reported Outcomes for Appearance of 
Eyebrows, Appearance of Eyelashes, Eye Irritation, 
and Nail Appearance.................................................................................62
9.1.2.2.
Other Clinician-Reported Outcomes for Eyebrow Hair 
Loss, Eyelash Hair Loss, and Nail Appearance ...............................................63
9.1.3.
Health Outcomes and Quality-of-Life Measures...................................................63
9.1.3.1.
Skindex-16 Adapted for Alopecia Areata........................................................63
9.1.3.2.
Medical Outcomes Study 36-Item Short-Form Health 
Survey Version 2 Acute..................................................................................63
9.1.3.3.
EQ-5D-5L ......................................................................................................63
9.1.3.4.
Hospital Anxiety and Depression Scale ..........................................................64
9.1.4.
Alopecia Areata Investigator Global Assessment .................................................64
9.1.5.
Appropriateness of Assessments ..........................................................................64
9.2.
Adverse Events ............................................................................................................64
9.2.1.
Serious Adverse Events........................................................................................65

I4V-MC-JAIR(d) Clinical Protocol
Page 4
LY3009104
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................66
9.2.2.
Adverse Events of Special Interest .......................................................................66
9.2.3.
Complaint Handling.............................................................................................66
9.3.
Treatment of Overdose.................................................................................................67
9.4.
Safety...........................................................................................................................67
9.4.1.
Electrocardiograms ..............................................................................................67
9.4.2.
Vital Signs ...........................................................................................................67
9.4.3.
Physical Examination...........................................................................................67
9.4.4.
Laboratory Tests ..................................................................................................67
9.4.5.
Columbia Suicide Severity Rating Scale...............................................................67
9.4.6.
Self-Harm and Follow-Up Supplement Forms......................................................68
9.4.7.
Chest X-Ray and Tuberculosis Testing.................................................................68
9.4.8.
Hepatitis B Virus DNA Monitoring......................................................................68
9.4.9.
Venous Thromboembolism Assessment ...............................................................69
9.4.10.
Safety Monitoring ................................................................................................69
9.4.10.1.
Hepatic Safety Monitoring..............................................................................70
9.5.
Pharmacokinetics .........................................................................................................70
9.6.
Pharmacodynamics ......................................................................................................71
9.7.
Pharmacogenomics ......................................................................................................71
9.7.1.
Whole Blood Samples for Pharmacogenetic Research..........................................71
9.8.
Biomarkers...................................................................................................................71
9.9.
Medical Resource Utilization and Health Economics ...................................................72
10.
Statistical Considerations ..................................................................................................73
10.1. Sample Size Determination ..........................................................................................73
10.2. Populations for Analyses..............................................................................................74
10.3. Statistical Analyses ......................................................................................................74
10.3.1.
General Statistical Considerations ........................................................................74
10.3.1.1.
Analysis Methods...........................................................................................75
10.3.1.2.
Missing Data Imputation ................................................................................76
10.3.1.3.
Multiple Comparisons/Multiplicity.................................................................77
10.3.2.
Treatment Group Comparability...........................................................................80
10.3.2.1.
Patient Disposition..........................................................................................80
10.3.2.2.
Patient Characteristics ....................................................................................80
10.3.2.3.
Concomitant Therapy .....................................................................................80
10.3.2.4.
Treatment Compliance....................................................................................80
10.3.3.
Efficacy Analyses ................................................................................................81
10.3.3.1.
Primary Analyses ...........................................................................................81
10.3.3.2.
Secondary Analyses........................................................................................81

I4V-MC-JAIR(d) Clinical Protocol
Page 5
LY3009104
10.3.3.3.
Exploratory Analyses .....................................................................................81
10.3.4.
Safety Analyses....................................................................................................81
10.3.5.
Other Analyses.....................................................................................................82
10.3.5.1.
Subgroup Analyses.........................................................................................82
10.3.6.
Interim Analyses..................................................................................................82
10.3.6.1.
Data Monitoring Committee ...........................................................................82
10.3.6.2.
Adjudication Committee.................................................................................83
10.3.6.3.
Week 36 Primary Outcomes Analyses and Other Interim 
Analyses.........................................................................................................83
11.
References ........................................................................................................................84
12.
Appendices .......................................................................................................................87

I4V-MC-JAIR(d) Clinical Protocol
Page 6
LY3009104
List of Tables
Table
Page
Table JAIR.1.
Schedule of Activities....................................................................................18
Table JAIR.2.
Objectives and Endpoints...............................................................................29
Table JAIR.3.
Treatment Regimens......................................................................................51
Table JAIR.4.
Criteria for Temporary Interruption of Investigational Product.......................59

I4V-MC-JAIR(d) Clinical Protocol
Page 7
LY3009104
List of Figures
Figure
Page
Figure JAIR.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIR.....................34
Figure JAIR.2.
Graphical testing procedure for Clinical Protocol I4V-MC-JAIR. ..................78

I4V-MC-JAIR(d) Clinical Protocol
Page 8
LY3009104
List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................88
Appendix 2.
Clinical Laboratory Tests...............................................................................93
Appendix 3.
Study Governance Considerations..................................................................95
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................99
Appendix 5.
Liver Function Testing and Hepatic Safety Monitoring................................100
Appendix 6.
Additional Information on Statistical Methods.............................................101
Appendix 7.
Monitoring Tests for Confirmed VTE..........................................................105
Appendix 8.
Provisions for Changes in Study Conduct During Exceptional 
Circumstances .............................................................................................106
Appendix 9.
Protocol Amendment I4V-MC-JAIR(d) Summary A Multicenter, 
Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to 
Evaluate the Efficacy and Safety of Baricitinib in Adult Patients with
Severe or Very Severe Alopecia Areata (BRAVE-AA2)..............................110

I4V-MC-JAIR(d) Clinical Protocol
Page 9
LY3009104
1. Synopsis
Title of Study:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 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 (Colón 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 (Janković 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 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 
(Xing et al. 2014; Mackay-Wiggan et al. 2016; Craiglow et al. 2017; Liu et al. 2017; Jabbari 
et al. 2018; Liu and King 2018).  Results from the interim analysis of the Phase 2 portion of the 
ongoing IV4-MC-JAHO (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 and 16 weeks of 
treatment with no new safety signal.  This Phase 3, placebo-controlled study will evaluate the 
efficacy and safety of baricitinib 2-mg QD and 4-mg QD for the treatment of severe (Severity of 
Alopecia Tool [SALT] score of 50%-94%) and very severe AA (SALT score of 95%-100%).  
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%-
100%) of the scalp.
This clinical program currently comprises 2 trials:

Study JAHO 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: 1-mg 
once daily (QD), 2-mg QD, and 4-mg QD.  The results of the interim analysis of the 
Phase 2 portion confirmed the potential of baricitinib to restore hair growth and 

I4V-MC-JAIR(d) Clinical Protocol
Page 10
LY3009104
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.

Study I4V-MC-JAIR (JAIR), described in this protocol, is also a double-blind, 
placebo-controlled Phase 3 trial and will evaluate the same 2-mg QD and 4-mg QD 
dose regimens.
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).
During the long term extension (Period 3), eligible patients will be able to participate in a 
randomized downtitration.  The objective of the randomized downtitration is to evaluate the 
possibility of maintaining efficacy with a lower dose of baricitinib in eligible responder patients 
(SALT ≤20).
Objective(s)/Endpoints:
Objectives
Endpoints
Primary Objective 
These are pre-specified objectives that will be adjusted for multiplicity.
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 dose or 
2-mg dose 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 SALT50Week 12

Proportion of patients achieving  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 dose or 
2-mg dose 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

I4V-MC-JAIR(d) Clinical Protocol
Page 11
LY3009104
Objectives
Endpoints
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 dose or 
2-mg dose 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 SALT75 at Weeks 24 and 
36

Proportion of patients achieving 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 
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 dose or 
2-mg dose 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 at Weeks 24 and 36
in Skindex-16 AA domain scores (Symptoms, 
Emotions, Functioning)

Mean change from Baseline in HADS-A and HADS-D 
total scores at Weeks 24 and 36  

I4V-MC-JAIR(d) Clinical Protocol
Page 12
LY3009104
Objectives
Endpoints
Other Secondary (Patients entering Randomized Downtitration)
These are pre-specified objectives that will NOT be adjusted for multiplicity.
To compare the maintenance of efficacy for patients 
randomized to remain on 4-mg of baricitinib, 
compared with patients randomized to 2-mg of 
baricitinib 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 2-mg of baricitinib 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
4-mg

Percent change in SALT score at 12, 16, 24, and 
36 weeks of retreatment with baricitinib 4-mg

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 4-mg
Abbreviations:  AA = alopecia areata; ClinRO = clinician-reported outcome; EB = eyebrow; EL = eyelash;
HADS = Hospital Anxiety and Depression Scale; PRO = patient-reported outcome; SALT = Severity of Alopecia 
Tool; 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; Skindex-16 AA = Skindex-16 Adapted for 
Alopecia Areata.
Summary of Study Design:  
Study I4V-MC-JAIR (JAIR) is a Phase 3, multicenter, randomized, double-blind, 
placebo-controlled, parallel-group study.  Efficacy and safety of baricitinib 2-mg QD and 4-mg 
QD will be compared to placebo in adult patients with severe (SALT score of 50%-94%) or very 
severe (SALT score of 95%-100%) scalp AA.  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.  The study design is divided into 5 periods:  a 5-week 
screening period, a 36-week double-blind, placebo-controlled treatment period, a 68-week long-
term extension period that includes a randomized downtitration of baricitinib, a 96-week 
bridging extension, and a posttreatment follow-up period.

I4V-MC-JAIR(d) Clinical Protocol
Page 13
LY3009104
Approximately 476 adult patients will be randomized in a 2:2:3 ratio to receive placebo once 
daily (QD), baricitinib 2-mg dose QD, or baricitinib 4-mg dose QD.  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).
Treatment Arms and Duration:  
At Baseline, patients will be randomized in a 2:2:3 ratio to receive placebo QD, baricitinib 2-mg
dose QD, or baricitinib 4-mg dose QD for up to 200 weeks.
Number of Patients:
Approximately 476 participants will be enrolled, and approximately 678 patients will be 
screened to achieve this enrollment.
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.  

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 
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) (ie, 4 weeks 
after Week 200 (Visit 24) or the Early Termination Visit [ET]). 
Note:  Patients who have discontinued IP product but remain in the study for more than 
28 days without IP will have an ET visit if they choose to discontinue early; however, a 
separate follow up visit (Visit 801) 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

Patients in the placebo treatment arm who have not achieved a SALT ≤20 at Week 36 
will be rescued to baricitinib and randomized in a 1:1 ratio to baricitinib 2-mg dose or 
baricitinib 4-mg dose.

Patients in the placebo arm who have achieved a SALT ≤20 at Week 36 will remain on 
placebo.  These patients who have experienced spontaneous regrowth will remain on 

I4V-MC-JAIR(d) Clinical Protocol
Page 14
LY3009104
placebo until Week 52, even if a relapse is observed between Week 36 and Week 52 
(refer to Week 52 for rescue of placebo patients who experience a loss of treatment 
benefit).

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 the 4-mg dose baricitinib treatment arm who achieve a SALT ≤20 at Week 52 
(responders) are eligible for randomized downtitration, provided that they have stayed on 
the same dose of baricitinib from initial randomization (Visit 2).

Patients who were rescued to baricitinib at Week 36 and patients randomized to 2-mg
dose baricitinib will not be eligible for randomized downtitration and will remain in their 
same treatment group.

Eligible patients will be automatically randomized in a blinded manner by the interactive 
web-response system (IWRS) in a 1:1 ratio to either stay on their current 4-mg dose of 
baricitinib or transition to 2-mg dose of baricitinib (randomized downtitration).

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 2-mg dose of baricitinib at Week 52 (randomized 
downtitration), will be automatically retreated with the 4-mg dose of baricitinib,
as randomized at Baseline (Visit 2).
o
remained on 4-mg dose of baricitinib at Week 52 (randomized downtitration), will 
continue to receive the same dose of baricitinib.
o
were randomized to 2-mg dose at Baseline (Visit 2), will be rescued to 4-mg dose.
o
had remained on placebo since Baseline (Visit 2), will be rescued to baricitinib 
2-mg.
Note:  An unscheduled visit may be used to assess the patient who reports a loss of treatment 
benefit (see SOA [Section 2] for detailed requirements).

I4V-MC-JAIR(d) Clinical Protocol
Page 15
LY3009104
Nonresponders (SALT  >20)

Patients who have been in the baricitinib 4-mg dose 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 dose 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 dose treatment group from Baseline will be 
rescued to baricitinib 4-mg dose.

Those who were rescued to baricitinib at Week 36, will continue in their current 
treatment arm at Week 52.

Those who were randomized to placebo at Baseline and were not eligible for rescue to 
baricitinib at Week 36 (spontaneous remission) will be rescued to baricitinib 2-mg. 
Note: Investigators should consider discontinuing patients who do not present any 
improvement of AA lesions by Week 64 (Visit 14).
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:
Unless otherwise specified, the efficacy and health outcome analyses of the study will be 
conducted on the Full Analysis Set (FAS) or other populations described in the statistical 
analysis plan (SAP).  Safety analyses will be conducted on safety population. 
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 time point of interest for any 
reason.  Additional analyses may be performed and will be described in detail in the SAP for 
patients who discontinued the study and for patients missing measurements prior to a fixed time 
point. 
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 

I4V-MC-JAIR(d) Clinical Protocol
Page 16
LY3009104
otherwise stated. Type III tests for LS means will be used for statistical comparison between 
treatment groups. The LS mean difference, standard error, p-value, and 95% CI may also be 
reported. Additional efficacy or safety interim analyses may be performed prior to final database 
lock (F-DBL) to support regulatory submission 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.  
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, discontinuation, and other categorical safety 
data.  Continuous vital signs and laboratory values will be analyzed by an analysis of covariance 
(ANCOVA) with treatment and Baseline values in the model.  

I4V-MC-JAIR(d) Clinical Protocol
Page 17
LY3009104
2. Schedule of Activities
The Schedule of Activities described below should be followed for all participants enrolled in
Study I4V-MC-JAIR (JAIR).  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.

I4V-MC-JAIR(d) Clinical Protocol
Page 18
LY3009104
Table JAIR.1.
Schedule of Activities
Screeni
ng
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
801b
Weeks from 
Randomization
0
4
8
12
16
24
36
40
44
52
56
60
64
68
76
88
10
4
120
136
152
168
184
200
Period 
2 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
Xc
Xc
Clinical 
Assessments
Demographics 
X
Preexisting 
Conditions/Medic
al History
X
MPHL/FPHL 
Historyd
X
Substance Use 
(alcohol, tobacco)
X
Previous and 
Current AA 
Treatments
X
Chest x-ray
(posterior-
anterior view)e
X
TB testf
X
Read PPD if 
applicable 
(48-72 hours after 
V1)g
X
Physical 
Examination
X
12-lead ECG 
(single, local)
X

I4V-MC-JAIR(d) Clinical Protocol
Page 19
LY3009104
Screeni
ng
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
801b
Weeks from 
Randomization
0
4
8
12
16
24
36
40
44
52
56
60
64
68
76
88
10
4
120
136
152
168
184
200
Period 
2 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
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 
Examh
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 
assessmentd
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
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 
assessed 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Scales/Questionn
aires
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 Scaled
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

I4V-MC-JAIR(d) Clinical Protocol
Page 20
LY3009104
Screeni
ng
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
801b
Weeks from 
Randomization
0
4
8
12
16
24
36
40
44
52
56
60
64
68
76
88
10
4
120
136
152
168
184
200
Period 
2 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
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
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
X
X
X
X
X
X
X
X
X
X
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

I4V-MC-JAIR(d) Clinical Protocol
Page 21
LY3009104
Screeni
ng
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
801b
Weeks from 
Randomization
0
4
8
12
16
24
36
40
44
52
56
60
64
68
76
88
10
4
120
136
152
168
184
200
Period 
2 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
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
Pharmacogenetics
:  blood
X
Serum 
immunoglobulin 
(IgE)
X
X
X
X
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

I4V-MC-JAIR(d) Clinical Protocol
Page 22
LY3009104
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; ET = early termination; EQ-
5D-5L = European Quality of Life – 5 Dimensions – 5 Level; 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 = interactive web-response system; MPHL = male 
pattern hair loss; 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 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 Section 5.1.3). Not applicable to unscheduled visits conducted for other reasons.
b
Visit 801 (Posttreatment Follow-Up Period) 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.
c
See Section 5.1.3 for details on the randomization of placebo non-responders at Week 36 and of eligible baricitinib 4-mg responders at Week 52.
d
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.  
e
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.
f
TB test(s) including PPD, QuantiFERON®-TB Gold, and T SPOT®.TB.  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 
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.
g
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).
h
The symptom-directed physical examination may be repeated at the investigator’s discretion any time a patient presents with physical complaints.
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).

I4V-MC-JAIR(d) Clinical Protocol
Page 23
LY3009104
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 24
LY3009104
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 (Janković 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 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 
(Xing et al. 2014; Mackay-Wiggan et al. 2016; Craiglow et al. 2017; Liu et al. 2017; Jabbari 
et al. 2018; Liu and King 2018). Results from the interim analysis of the Phase 2 portion of the 
ongoing IV4-MC-JAHO (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 and 16 weeks of 
treatment with no new safety signal.
Lilly has initiated a clinical program to evaluate the efficacy and safety of baricitinib in adult 
patients with severe (Severity of Alopecia Tool [SALT] score of 50%-94%) and very severe AA 
(SALT score of 95%-100%) of the scalp.
This clinical program currently comprises 2 trials:

Study JAHO 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: 1-mg once daily (QD), 
2-mg QD, and 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.

Study I4V-MC-JAIR (JAIR), described in this protocol, is also a double-blind, 
placebo-controlled Phase 3 trial and will evaluate the same doses regimens.

I4V-MC-JAIR(d) Clinical Protocol
Page 25
LY3009104
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).
During the long-term extension (Period 3), eligible patients will be able to participate in a 
randomized downtitration.  The objective of the randomized downtitration is to evaluate the 
possibility of maintaining efficacy with a lower dose of baricitinib in eligible responder patients 
(SALT ≤20 ).
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 areata totalis [AT]), or extend to complete hair loss of head and body (alopecia areata 
universalis [AU]) ( Olsen et al. 1999, 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 (Janković 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 

I4V-MC-JAIR(d) Clinical Protocol
Page 26
LY3009104
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 (IL)-15 
(Islam et al. 2015; Strazzulla et al. 2018) accompanied by additional cytokines including 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 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%-94%) or very severe 
AA (SALT score of 95%-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 and King 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 the ongoing JAHO study 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 at the 2-mg dose and 4-mg doses by a second 
interim analysis of the Phase 2 portion of Study JAHO where the 2-mg dose and 4-mg dose were 
statistically significantly superior to placebo for the primary endpoint (SALT score ≤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 event (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 

I4V-MC-JAIR(d) Clinical Protocol
Page 27
LY3009104
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 be offered to 
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 this 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 (ie, 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 28
LY3009104
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 and very severe AA is assessed to be favorable.
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).

I4V-MC-JAIR(d) Clinical Protocol
Page 29
LY3009104
4.
Objectives and Endpoints
Table JAIR.2 shows the objectives and endpoints of the study.
Table JAIR.2.
Objectives and Endpoints
Objectives
Endpoints
Primary Objective 
These are pre-specified objectives that will be adjusted for multiplicity.
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 dose 
or 2-mg dose 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 SALT50 at Week 12

Proportion of patients achieving 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 dose 
or 2-mg dose 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

I4V-MC-JAIR(d) Clinical Protocol
Page 30
LY3009104
Objectives
Endpoints
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 dose 
or 2-mg dose 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 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 
baseline at Week 16 and 24, (among patients with 
ClinRO Measure for EL Hair Loss ≥2 at Baseline)
To compare the efficacy of baricitinib 4-mg dose 
or 2-mg dose 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 at Weeks 24 and 36 in 
Skindex-16 AA domain scores (Symptoms, Emotions, 
Functioning)

Mean change from Baseline in HADS-A and HADS-D 
total scores at Weeks 24 and 36  

I4V-MC-JAIR(d) Clinical Protocol
Page 31
LY3009104
Objectives
Endpoints
Other Secondary (Patients entering Randomized Downtitration)
These are pre-specified objectives that will NOT be adjusted for multiplicity.
To compare the maintenance of efficacy for 
patients randomized to remain on 4-mg of 
baricitinib, compared with patients randomized to 
2-mg of baricitinib 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 2-mg of baricitinib 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
4-mg

Percent change in SALT score at 12, 16, 24, and 
36 weeks of retreatment with baricitinib 4-mg

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 4-mg
Exploratory Objectives may include evaluating the response to baricitinib treatment regimens on clinical measures 
and PROs.  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, 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.  
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 32
LY3009104
5. Study Design
5.1.
Overall Design
Study I4V-MC-JAIR (JAIR) is a Phase 3, multicenter, randomized, double-blind, 
placebo-controlled, parallel-group study evaluating the efficacy and safety of baricitinib 2-mg 
QD and 4-mg QD in adult patients with severe (SALT score of 50%-94%) or very severe (SALT 
score of 95%-100%) scalp AA.  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.  The study design is divided into 5 periods:  a 5-week screening period, a 36-week 
double-blind, placebo-controlled treatment period, a 68-week long-term extension period that 
includes a randomized downtitration of baricitinib, a 96-week bridging extension, and a 
posttreatment follow-up period.  
Approximately 476 adult patients will be randomized in a 2:2:3 ratio to receive placebo once 
daily (QD), baricitinib 2-mg dose QD, or baricitinib 4-mg dose QD.  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).
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 10.3.6 outlines information regarding the interim analysis.
Figure JAIR.1 illustrates the study design.  The full visit schedule is outlined in the SOA 
(Section 2).

I4V-MC-JAIR(d) Clinical Protocol
Page 33
LY3009104
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; SALT = Severity of Alopecia Tool; V = Visit.

I4V-MC-JAIR(d) Clinical Protocol
Page 34
LY3009104
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 dose 
or baricitinib 4-mg dose.  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 an IGA 0 or 1 will remain on placebo at Week 36.
d
At Week 52, responders (SALT ≤20) in the baricitinib 4-mg treatment group who are eligible (ie, stayed on the same dose of baricitinib from initial 
randomization at Visit 2) will be randomized in a 1:1 ratio to either stay on baricitinib 4-mg or transition to baricitinib 2-mg (randomized downtitration).  See 
Section 5.1.3 for more details.
e
Patients who have been in the baricitinib 4-mg dose 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.  
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 5.1.3 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 baricitinib 
2-mg at Week 52 (randomized downtitration) will be retreated with baricitinib 4-mg, as randomized at Baseline (Visit 2).  Patients who were randomized to 
remain on baricitinib 4-mg (randomized downtitration) will continue to receive the same dose of baricitinib. See Section 5.1.3 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 were randomized to placebo at Baseline and were not eligible for rescue to baricitinib at Week 36 (due to spontaneous remission) will be 
rescued to baricitinib 2-mg if they are nonresponders at Week 52 (AA-IGA ≥2) or experience a loss of treatment benefit after Week 52 (>20-point absolute 
worsening in SALT score).
k
Week 52 nonresponders who have been in the baricitinib 2-mg dose treatment group from Baseline will be rescued to baricitinib 4-mg dose.  Responders who 
have been in the baricitinib 2-mg dose treatment group from Baseline who experience a loss of treatment benefit after Week 52 (>20-point absolute 
worsening in SALT score) will be rescued to baricitinib 4-mg.
Figure JAIR.1.
Illustration of study design for Clinical Protocol I4V-MC-JAIR.

I4V-MC-JAIR(d) Clinical Protocol
Page 35
LY3009104
5.1.1. 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 Criterion [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 nonlive 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.
5.1.2. 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). 
At Visit 2, after laboratory samples are collected and all assessments are completed, patients will 
take the first dose of IP in the clinic. 
Patients will be randomized in a 2:2:3 ratio to receive placebo QD, baricitinib 2-mg dose QD, or 
baricitinib 4-mg dose QD. 
During Study Period 2 (double-blind treatment), medications listed in Section 7.7.2 will be 
prohibited.  
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).
5.1.3. 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.
During Study Period 3 (long-term extension), medications listed in Section 7.7.2 will be 
prohibited.  

I4V-MC-JAIR(d) Clinical Protocol
Page 36
LY3009104
At Week 36 

Patients in the placebo treatment arm who have not achieved SALT ≤20 at Week 36 will 
be rescued to baricitinib and randomized in a 1:1 ratio to baricitinib 2-mg dose or 
baricitinib 4-mg dose.

Patients in the placebo arm who have achieved a SALT ≤20 at Week 36 will remain on 
placebo.  Those patients who have experienced spontaneous regrowth will remain on 
placebo until Week 52, even if a relapse is observed between Week 36 and Week 52. 
(Refer to Week 52 for rescue of placebo patients who experience a loss of treatment 
benefit).

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 the 4-mg dose baricitinib treatment arm who achieve a SALT ≤20 at Week 52 
(responders) are eligible for randomized downtitration, provided that they have stayed on 
the same dose of baricitinib from initial randomization (Visit 2).  

Patients who were rescued to baricitinib at Week 36 and patients randomized to 2-mg
dose baricitinib will not be eligible for randomized downtitration and will remain in their 
same treatment group.  

Eligible patients will be automatically randomized in a blinded manner by the interactive 
web-response system (IWRS) in a 1:1 ratio to either stay on their current 4-mg dose of 
baricitinib or transition to 2-mg dose of baricitinib (randomized downtitration).  

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 2-mg dose of baricitinib at Week 52 (randomized 
downtitration), will be automatically retreated with the 4-mg dose of baricitinib,
as randomized at Baseline (Visit 2).
o
remained on 4-mg dose of baricitinib at Week 52 (randomized downtitration), will 
continue to receive the same dose of baricitinib.
o
were randomized to 2-mg dose at Baseline (Visit 2), will be rescued to 4-mg dose.
o
had remained on placebo since Baseline (Visit 2), will be rescued to baricitinib 
2-mg.

I4V-MC-JAIR(d) Clinical Protocol
Page 37
LY3009104
Note:  An unscheduled visit may be used to assess the patient who reports a loss of treatment 
benefit (see SOA [Section 2] for detailed requirements).
Nonresponders (SALT >20)

Patients who have been in the baricitinib 4-mg dose 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 dose 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 dose treatment group from Baseline will be 
rescued to baricitinib 4-mg dose.

Those who were rescued to baricitinib at Week 36 will continue in their current treatment 
arm at Week 52.

Those who were randomized to placebo at Baseline and were not eligible for rescue to 
baricitinib at Week 36 (spontaneous remission) will be rescued to baricitinib 2-mg.
Note: Investigators should consider discontinuing patients who do not present any 
improvement of AA lesions by Week 64 (Visit 14).
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.
5.1.4. Period 4:  Bridging Extension
Patients who have completed Week 104 and have not met criteria for permanent discontinuation 
will have the possibility to remain in the trial for up to 96 additional weeks (up to Week 200).
During Period 4, patients will continue to receive the same treatment they received during Period 
3.
Patients who were randomized to placebo at Baseline and were not eligible for rescue to 
baricitinib at Week 36 or during Period 3 (spontaneous remission) will continue to have the 
opportunity to be rescued to baricitinib 2-mg if they experience loss of treatment benefit.
Baricitinib 4mg responders who had been randomized to baricitinib 2-mg at Week 52 
(randomized downtitration) and have remained on baricitinib 2-mg, will have the possibility to 
be retreated with baricitinib 4-mg if they experience a loss of benefit (defined as >20-point 
absolute worsening in total SALT score) during Period 4.
5.1.5. 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 

I4V-MC-JAIR(d) Clinical Protocol
Page 38
LY3009104
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 early termination (ET) visit, 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 visit if they choose to discontinue early; however, a separate follow-up visit 
(Visit 801) is not required.
5.2.
Number of Participants
Approximately 476 participants will be enrolled, and approximately 678 patients will be 
screened to achieve this enrollment.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure shown in the 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 Study JAHO confirm the potential of 
baricitinib to restore hair growth in patients suffering from AA.
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%-94%) and very 
severe AA (defined as a SALT score of 95%-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 (4-mg
dose and 2-mg dose) 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 39
LY3009104
The primary endpoint is the proportion of patients reaching a SALT ≤20 (ie, ≤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 
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 baricitinib 4-mg dose 
over 52 weeks, will be randomized to either stay on baricitinib 4-mg or transition to baricitinib 2-
mg dose (in a 1:1 ratio) to assess the possibility to maintain efficacy with a lower dose.  These 
patients will be retreated with baricitinib 4-mg if they present with a loss of treatment benefit 
(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.
5.5.
Justification for Dose
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 have been
included in the Phase 2 part of Study I4V-MC-JAHO (JAHO), including a 1-mg dose, to cover 
the range of exposures where clinical responses could be anticipated. The results of the 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 with the 2-mg dose. This observation will need to be confirmed on 
larger sample sizes. These results were confirmed at the 2-mg dose and 4-mg dose by the second 
interim analysis of Phase 2 portion of Study JAHO conducted after 36 weeks of treatment.  
There were no SAEs during the period of treatment and no new safety findings.

I4V-MC-JAIR(d) Clinical Protocol
Page 40
LY3009104
The pharmacokinetic (PK) 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 regimens
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 
estimated glomerular filtration rate (eGFR) 60 to <90 mL/min/1.73 m2 and eGFR 30 to 
<60 mL/min/1.73 m2, respectively), dose adjustment is not required for patients with eGFR 
≥60 mL/min/1.73 m2.  Patients with eGFR <60 mL/min/1.73 m2 who are randomized to the 4-mg 
dose will receive a dose of 2-mg QD, which will ensure that exposures do not exceed those of 
the 4-mg QD dose in patients with eGFR ≥60 mL/min/1.73 m2.  For patients randomized to the 
2-mg dose, 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 41
LY3009104
6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
Study investigator(s) will review patient history and screening test results at Visit 1 and Visit 2 to 
determine if the patient meets all inclusion 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 (ie, 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 the following:
a.
Systemic therapies (eg, methotrexate, cyclosporine, corticosteroids, JAK 
inhibitors, apremilast, dimethyl fumarate derivatives, hydroxychloroquine, 
mycophenolate-mofetil, IFNγ, azathioprine) and biologics (eg, monoclonal 
antibodies) 

I4V-MC-JAIR(d) Clinical Protocol
Page 42
LY3009104
b. Intralesional corticosteroid injections
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 are 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). 

I4V-MC-JAIR(d) Clinical Protocol
Page 43
LY3009104

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 (ie, 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

I4V-MC-JAIR(d) Clinical Protocol
Page 44
LY3009104
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” (eg, 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.
k.
Immunosuppressants (eg, 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

I4V-MC-JAIR(d) Clinical Protocol
Page 45
LY3009104
[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.
[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).

I4V-MC-JAIR(d) Clinical Protocol
Page 46
LY3009104
c.
Symptomatic herpes simplex at the time of randomization.
d. Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C 
virus (HCV), or human immunodeficiency virus (HIV).
e.
Household contact with a person with active tuberculosis (TB) and did not 
receive appropriate and documented prophylaxis for TB.
f.
Evidence of active TB or have previously had evidence of active TB and 
did not receive appropriate and documented treatment.
g. Clinically serious infection, or received 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:

I4V-MC-JAIR(d) Clinical Protocol
Page 47
LY3009104
a.
Question 4 (Active Suicidal Ideation with Some Intent to Act, Without 
Specific Plan) on the “Suicidal Ideation” portion of the Columbia Suicide 
Severity Rating Scale (C-SSRS); or
b. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the 
“Suicidal Ideation” portion of the C-SSRS; or 
c.
Any of the suicide-related behaviors (actual attempt, interrupted attempt, 
aborted attempt, preparatory act or behavior) on the “Suicidal Behavior”
portion of the C-SSRS;
and the ideation or behavior occurred within 2 months 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:

I4V-MC-JAIR(d) Clinical Protocol
Page 48
LY3009104
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 
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 49
LY3009104
[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.
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 (WBC) 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 [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 IP 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 50
LY3009104
[36] Have previously been randomized in this study or any other study 
investigating baricitinib.
[37] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, 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, blood products, or sperm 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 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 51
LY3009104
7. Treatments
7.1.
Treatments Administered
Study JAIR involves a comparison of placebo, baricitinib 2-mg, and baricitinib 4-mg 
administered orally once a day. Table JAIR.3 shows the treatment regimens and the 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, and

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 JAIR.3.
Treatment Regimens
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 Labeling
The Sponsor (or its designee) will provide the following IPs:

tablets containing 2-mg of baricitinib

tablets containing 4-mg of baricitinib

placebo tablets to match baricitinib 2-mg tablets, 4-mg tablets
Each tablet has a distinctive shape and color, 2-mg versus 4-mg, and each strength tablet has a 
matching placebo.  
Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized in a 2:2:3 ratio to receive 
double-blind treatment with placebo QD, baricitinib 2-mg dose QD, or baricitinib 4-mg dose QD 
at Visit 2 (Week 0).  Randomization will be stratified by geographic region (North America, 
Asia, and Rest of World) and duration of current episode at Baseline (less than 4 years versus at 

I4V-MC-JAIR(d) Clinical Protocol
Page 52
LY3009104
least 4 years) for the whole study.  Randomization for the randomized-downtitration 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. Patients 
enrolled 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) randomized to the 4-mg active treatment arm will receive a dose of 2-mg 
QD by the IWRS.  There will be no dose adjustment based on renal function for doses other than 
4-mg.
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 or 2-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 8.1.2).
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.
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 

I4V-MC-JAIR(d) Clinical Protocol
Page 53
LY3009104
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 
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 (CRP) for the patient to 
continue in the study.
7.4.
Dosage Modification
As described in Section 5.1.3, some patients may be eligible for rescue to baricitinib at Week 36 
and transition to 4-mg or 2-mg doses of baricitinib 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 per bottle.  
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 54
LY3009104
Patients’ compliance will be further defined in the statistical analysis plan (SAP).
7.7.
Concomitant Therapy
All concomitant medication, whether prescription or over-the-counter, used at Baseline and/or 
during the course of the study, must be recorded on the Concomitant Medication electronic case 
report form (eCRF).  Patients will be instructed to consult the investigator or other appropriate 
study personnel at the site before taking any new medications or supplements during the study.  
For 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” (eg, 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, intralesional, 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:

I4V-MC-JAIR(d) Clinical Protocol
Page 55
LY3009104
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.  

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 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 (eg,
monoclonal antibodies).

Any other AA treatment that has been inadvertently initiated and is not discontinued will 
lead to permanent discontinuation.
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 56
LY3009104
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 57
LY3009104
8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Permanent Discontinuation from Study Treatment
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 laboratory 
abnormalities are observed:

WBC 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 JAIR.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.

I4V-MC-JAIR(d) Clinical Protocol
Page 58
LY3009104
In addition, patients will be discontinued from IP in the following circumstances:

pregnancy

malignancy (except for successfully treated basal or squamous cell skin carcinoma)

HBV DNA is detected with a value above limit of quantitation (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 JAIR.4.  
For the abnormal laboratory findings and clinical events (regardless of relatedness) listed in 
Table JAIR.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 JAIR.4 may be restarted at the discretion of the investigator.

I4V-MC-JAIR(d) Clinical Protocol
Page 59
LY3009104
Table JAIR.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

I4V-MC-JAIR(d) Clinical Protocol
Page 60
LY3009104

A “yes” answer to any of the suicide-related behaviors (actual attempt, interrupted 
attempt, aborted attempt, preparatory act or behavior) on the “Suicidal Behavior” portion 
of the C-SSRS.  
NOTE:  Prior to resumption of IP, it is recommended that 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 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  

I4V-MC-JAIR(d) Clinical Protocol
Page 61
LY3009104

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 this protocol.
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 62
LY3009104
9.
Study Assessments and Procedures
Section 2 lists the SOA, 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 left side 
and right side of scalp 18% each, top constituting 40% of total surface, the posterior/back 24%.  
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. Scalp Hair Assessment PRO™
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 9.1.4.), the Scalp Hair Assessment 
PRO™is comprised of 5 categorical 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%-20% of my scalp is missing 
hair); 2 = A moderate area (21%-49% of my scalp is missing hair); 3 = A large area (50%-94% 
of my scalp is missing hair); and 4 = Nearly all or all (95%-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.

I4V-MC-JAIR(d) Clinical Protocol
Page 63
LY3009104
9.1.2.2.
Other Clinician-Reported Outcomes for Eyebrow Hair Loss, Eyelash Hair 
Loss, and Nail Appearance
Lilly has developed 3 other novel 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 outside of the US, 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
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 (Skindex-16 AA).  
It is composed of 16 items grouped under 3 domains:  Symptoms (4 items), Emotions (7 items), 
and Functioning (5 items).
9.1.3.2.
Medical Outcomes Study 36-Item Short-Form Health Survey Version 2 
Acute
The Short Form-36 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 European Quality of Life – 5 Dimensions – 5 Level (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 

I4V-MC-JAIR(d) Clinical Protocol
Page 64
LY3009104
EQ-5D-5L descriptive system, may be converted into a single summary index by applying a 
formula that essentially attaches values (also called weights) to each of the levels in each 
dimension (Herdman et al. 2011; EuroQoL 2015).
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 year (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. 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%-20%); 2 = Moderate (SALT score of 21%-49%); 3 = Severe 
(SALT score of 50%-94%); and 4 = Very Severe (SALT score of 95%-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 use in exploratory analysis.
9.1.5. 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]) and the health outcomes and quality of life measures 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 65
LY3009104
Lack of drug effect is not an AE in clinical studies because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record, via eCRF, the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs. Investigators should record their assessment of the 
potential relatedness of each AE to 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 (ie, 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 66
LY3009104
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a Sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.  Patients with a serious hepatic AE should have additional data collected using the 
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 (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.

I4V-MC-JAIR(d) Clinical Protocol
Page 67
LY3009104
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.
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 

I4V-MC-JAIR(d) Clinical Protocol
Page 68
LY3009104
group for the purpose of being a counterpart to the Columbia Classification Algorithm of Suicide 
Assessment categorization of suicidal events.  For this study, the scale has been adapted (with 
permission from the scale authors) to include only the portion of the scale that captures the 
occurrence of the 11 preferred ideation and behavior categories.
The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS, but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
9.4.6. Self-Harm and Follow-Up Supplement Forms
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the self-harm follow-up form.  The self-harm 
follow-up form is a series of questions that provides a more detailed description of the behavior 
cases.
9.4.7. 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.  

I4V-MC-JAIR(d) Clinical Protocol
Page 69
LY3009104

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 10.3.6.2).
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 10.3.6]).
The Lilly CRP will monitor safety data throughout the course of the study.  Lilly will review 
SAEs within time frames mandated by company procedures.  The Lilly CRP will, as is 
appropriate, consult with the functionally independent Global Patient Safety (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.

I4V-MC-JAIR(d) Clinical Protocol
Page 70
LY3009104
Investigators will monitor vital signs and carefully review findings that may be associated with 
cardiovascular events and VTE.  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
Not applicable.

I4V-MC-JAIR(d) Clinical Protocol
Page 71
LY3009104
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 to 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 
becomes commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome-wide association studies, and candidate gene studies.  Regardless of 
technology utilized 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 
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.  

I4V-MC-JAIR(d) Clinical Protocol
Page 72
LY3009104
Samples will be retained at a facility selected by Lilly for a maximum of 15 years after the last 
patient visit for the study, or for a shorter period if local regulations and ERBs impose shorter 
time limits.  This retention period enables use of new technologies, response to regulatory 
questions, and investigation of variable response that may not be observed until later in the 
development of baricitinib 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 73
LY3009104
10. Statistical Considerations
10.1. Sample Size Determination
Approximately 678 patients will be screened in order to enroll approximately 476 patients in 
Study JAIR.  The enrolled patients will be randomized in a 2:2:3 ratio for placebo QD 
(approximately 136 subjects), baricitinib 2-mg dose QD (approximately 136 subjects), or
baricitinib 4-mg dose QD (approximately 204 subjects).  This sample size will provide 
approximately 90% power to test the superiority of baricitinib 4-mg dose to placebo or the 
superiority of baricitinib 2-mg dose 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 the 4-mg dose and 0.01 for the 2-mg
dose. The assumptions used for the power calculation are as follows: 30% response rate for 
baricitinib 4-mg dose, 20% response rate for baricitinib 2-mg dose, 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 a SALT ≤20 at Week 52 (responders) AND who have remained on the 4-
mg dose of baricitinib from randomization (Visit 2) to Week 52, will enter the randomized 
downtitration, which is meant to evaluate the change in clinical response after treatment 
downtitration, and does not account for whether the sample size is sufficient to detect statistical
difference between baricitinib 4-mg dose and 2-mg dose. It is expected that there would be 
approximately 60 patients eligible for the randomized downtitration. 

I4V-MC-JAIR(d) Clinical Protocol
Page 74
LY3009104
10.2. Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Full Analysis Set (FAS)
All patients randomized in Study JAIR will be included in the FAS.  Patients 
will be analyzed according to the IP to which they were randomized at Baseline 
(Visit 2). Of note, FAS is essentially the ITT population.
Modified Full Analysis Set
(mFAS) Population 
All patients randomized in Study JAIR 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 patients who were randomized in 
Study JAIR, who received at least 1 dose of IP, and who did not discontinue 
from the study for the reason “Lost to Follow-up” at the first post-Baseline 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, 
ITT = intent-to-treat.
a
Some male patients with Grade IV AGA and female patients with patterned baldness may only be identified after 
hair regrowth.
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 efficacy analysis of the primary and key secondary endpoints will be conducted in the full 
analysis set (FAS) population.  All other efficacy or health outcome 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 may be 
performed prior to final database lock (F-DBL) to support regulatory submissions and will be 
described in detail 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 

I4V-MC-JAIR(d) Clinical Protocol
Page 75
LY3009104
methods described in the protocol (and the justification for making the change) will be described 
in the clinical study report (CSR).  Additional exploratory analyses of the data will be conducted,
as deemed appropriate.  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 nonresponder imputation (NRI), as described in Section 10.3.1.2.
The primary analyses for the continuous efficacy and health outcome variables will use 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 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 indication as very few patients experienced waxing 
and waning in scalp hair during the course of treatment from the Phase 2 portion of study JAHO
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 
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.  
Hazard ratio with CIs may be reported.  Kaplan-Meier curves will also be produced.  Diagnostic 

I4V-MC-JAIR(d) Clinical Protocol
Page 76
LY3009104
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 time 
point 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 time point 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 postbaseline assessment. The specific modification to the LOCF is data 
after permanent study treatment discontinuation will not be carried forward.

Mixed-effects 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 
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) will be included in the SAP. 

I4V-MC-JAIR(d) Clinical Protocol
Page 77
LY3009104
10.3.1.3. Multiple Comparisons/Multiplicity
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 JAIR.2 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 78
LY3009104
Figure JAIR.2.
Graphical testing procedure for Clinical Protocol I4V-MC-JAIR.
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 79
LY3009104
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 Secondary 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 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 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 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 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).

I4V-MC-JAIR(d) Clinical Protocol
Page 80
LY3009104

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 FAS population.  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 per bottle.  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 (ie, 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 

I4V-MC-JAIR(d) Clinical Protocol
Page 81
LY3009104
medication (ie, 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 score ≤20 (see 
Section 9.1.1) at Week 36.  The primary analysis testing the treatment difference between each 
of the baricitinib doses included in Study JAIR 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.  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 
(eg, lost to follow-up). Additional analysis of the primary efficacy outcome may be conducted 
and will include all available data up to 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 will include all available data up to 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 body system) 
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 82
LY3009104
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 post-Baseline 
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 time point. 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. Other Analyses
10.3.5.1. 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 
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. 
10.3.6. Interim Analyses
10.3.6.1. Data Monitoring Committee
A DMC will oversee the conduct of this trial.  The DMC will consist of members external to 
Lilly.  This DMC will follow the rules defined in the DMC charter, focusing on potential and 

I4V-MC-JAIR(d) Clinical Protocol
Page 83
LY3009104
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.
The DMC is authorized to evaluate unblinded interim efficacy and safety analyses during the 
study.  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.
10.3.6.2. 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.  
Details of membership, operations, recommendations from the Committee, and the 
communication plan will be documented in the Charter.
10.3.6.3. Week 36 Primary Outcomes Analyses and Other Interim Analyses
After all randomized patients 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, 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. 
Additional efficacy or safety interim analyses may occur after the PO-DBL and prior to the 
Final-DBL to support regulatory submissions and scientific disclosures and will be described in 
detail in the SAP.
Information that may unblind the study during the analyses will not be reported to study sites or 
blinded study team until the study has been unblinded.
Unblinding details will be specified in a separate unblinding plan document.

I4V-MC-JAIR(d) Clinical Protocol
Page 84
LY3009104
11.
References
Alosh M, Bretz F, Huque M. Advanced multiplicity adjustment methods in clinical trials. 
Stat Med. 2014;33(4):693-713.
Bretz F, Posch M, Glimm E, Klinglmueller F, Maurer W, Rohmeyer K. Graphical approaches for 
multiple comparison procedures using weighted Bonferroni, Simes, or parametric tests. Biom J.
2011;53(6):894-913.
Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors 
for inflammatory diseases. J Med Chem. 2014;57(12):5023-5038.
Colón EA, Popkin MK, Callies AL, Dessert NJ, Hordinsky MK. Lifetime prevalence of 
psychiatric disorders in patients with alopecia areata. Compr Psychiatry. 1991;32(3):245-251.
Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in 
adolescents. J Am Acad Dermatol. 2017;76(1):29-32.
EuroQol Group. EQ-5D-5L User Guide. Version 2.1. Available at:  
http://www.euroqol.org/fileadmin/user_upload/Documenten/PDF/Folders_Flyers/EQ-5D-
5L_UserGuide_2015.pdf. April 2015. Accessed March 2017.
Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, 
Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis G, 
Newton RC, Metcalf B, Friedman SM, Vaddi K. Selective inhibition of JAK1 and JAK2 is 
efficacious in rodent models of arthritis: preclinical characterization of INCB028050. 
J Immunol. 2010;184(9):5298-5307.
Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development 
and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 
2011;20(10):1727-1736.
Hordinsky M, Donati A. Alopecia areata: an evidence-based treatment update. Am J Clin 
Dermatol. 2014;15(3):231-246.
Hordinsky M, Junqueira AL. Alopecia areata update. Semin Cutan Med Surg. 2015;34(2):72-75.
Hunt N, McHale S. The psychological impact of alopecia. BMJ. 2005;331(7522):951-953.
Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a 
comprehensive review. Autoimmun Rev. 2015;14(2):81-89.
Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y, Sanchez GA, Goldbach-Mansky R, 
Christiano AM, Clynes R, Zlotogorski A. Reversal of alopecia areata following treatment with 
the JAK1/2 inhibitor baricitinib. EBioMedicine. 2015;2(4):351-355.
Jabbari A, Sansaricq F, Cerise J, Chen JC, Bitterman A, Ulerio G, Borbon J, Clynes R, 
Christiano AM, Mackay-Wiggan J. An open-label pilot study to evaluate the efficacy of 
tofacitinib in moderate to severe patch-type alopecia areata, totalis, and universalis. J Invest 
Dermatol. 2018:138(7):1539-1545.
Janković S, Perić J, Maksimović N, Ćirković A, Marinković J, Janković J, Reljić V, Medenica L. 
Quality of life in patients with alopecia areata: a hospital-based cross-sectional study. J Eur 
Acad Dermatol Venereol. 2016;30(5):840-846.

I4V-MC-JAIR(d) Clinical Protocol
Page 85
LY3009104
Karimkhani C, Boyers LN, Naghavi M, Coffeng LE, Lott JP, Wulf S, Hay R, Williams HC, 
Weinstock MA, Norton SA, Armstrong AW, Dunnick CA, Norris DA, Dellavalle RP. The 
global burden of disease associated with alopecia areata. Br J Dermatol. 2015;172(5):1424-
1426.
Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, Chen JC, Cerise JE, 
Jabbari A, Winge MC, Marinkovich MP, Christiano AM, Oro AE, King BA. Safety and 
efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight.
2016;1(15):e89776.
Korta DZ, Christiano AM, Bergfeld W, Duvic M, Ellison A, Fu J, Harris JE, Hordinsky MK, 
King B, Kranz D, Mackay-Wiggan J, McMichael A, Norris DA, Price V, Shapiro J, 
Atanaskova Mesinkovska N. Alopecia areata is a medical disease. J Am Acad Dermatol. 
2018;78(4):832-834.
Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric 
population. Pediatrics. 2008;122(4):812-824.
Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata 
and variants: a study of 90 patients. J Am Acad Dermatol. 2017;76(1):22-28.
Liu LY, King BA. Tofacitinib for the treatment of severe alopecia areata in adults and 
adolescents. J Investig Dermatol Symp Proc. 2018;19(1):S18-S20.
Liu LY, King BA, Craiglow BG. Health-related quality of life (HRQoL) among patients with 
alopecia areata (AA): a systematic review. J Am Acad Dermatol. 2016;75(4):806-812.
Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, Furniss M, Vaughan R, 
Christiano AM, Clynes R. Oral ruxolitinib induces hair regrowth in patients with moderate-to-
severe alopecia areata. JCI Insight. 2016;1(15):e89790.
Maruish ME. User’s manual for the SF-36v2 Health Survey (3rd ed.). Lincoln, RI: QualityMetric 
Incorporated. 2011.
Norwood OT. Male pattern baldness: classification and incidence. South Med J.
1975;68(11):1359–1365.
Olsen EA. Investigative guidelines for alopecia areata. Dermatol Ther. 2011;24(3):311-319.
Olsen EA, Bettencourt MS, Coté NL. The presence of loose anagen hairs obtained by hair pull in 
the normal population. J Investig Dermatol Symp Proc. 1999;4(3):258-260.
Olsen EA, Hordinsky MK, Price VH, Roberts JL, Shapiro J, Canfield D, Duvic M, King LE Jr, 
McMichael AJ, Randall VA, Turner ML, Sperling L, Whiting DA, Norris D; National 
Alopecia Areata Foundation. Alopecia areata investigational assessment guidelines – Part II. 
National Alopecia Areata Foundation. J Am Acad Dermatol. 2004;51(3):440-447.
Paus R, Nickoloff BJ, Ito T. A ‘hairy’ privilege. Trends Immunol. 2005;26(1):32-40.
Rencz F, Gulácsi L, Péntek M, Wikonkál N, Baji P, Brodszky V. Alopecia areata and health-
related quality of life: a systematic review and meta-analysis. Br J Dermatol. 
2016;175(3):561-571.
Snaith RP. The Hospital Anxiety and Depression Scale. Health Qual Life Outcomes. 2003;1:29.

I4V-MC-JAIR(d) Clinical Protocol
Page 86
LY3009104
Strazzulla LC, Wang EH, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J. Alopecia 
areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am 
Acad Dermatol. 2018;78(1):1-12.
Suárez-Fariñas M, Ungar B, Noda S, Shroff A, Mansouri Y, Fuentes-Duculan J, Czernik A, 
Zheng X, Estrada YD, Xu H, Peng X, Shemer A, Krueger JG, Lebwohl MG, Guttman-Yassky E.
Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel 
TH17/TH22 skewing. J Allergy Clin Immunol. 2015;136(5):1277-1287.
Tan E, Tay YK, Goh CL, Chin Giam Y. The pattern and profile of alopecia areata in Singapore –
a study of 219 Asians. Int J Dermatol. 2002;41(11):748-753.
Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic 
review. Clin Cosmet Investig Dermatol. 2015;8:397-403.
Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia areata. Int J Dermatol.
2007;46(2):121-131.
White D, Leach C, Sims R, Atkinson M, Cottrell D. Validation of the Hospital Anxiety and 
Depression Scale for use with adolescents. Br J Psychiatry. 1999;175:452-454.
Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, 
Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R. Alopecia 
areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med.
2014;20(9):1043-1049.
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 
1983;67(6):361-370.

I4V-MC-JAIR(d) Clinical Protocol
Page 87
LY3009104
12.
Appendices

I4V-MC-JAIR(d) Clinical Protocol
Page 88
LY3009104
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
AST
aspartate aminotransferase
AT
alopecia areata totalis
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
CI
confidence interval
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
ClinRO
clinician-reported outcome
CPK
creatinine phosphokinase
CRF
case report form

I4V-MC-JAIR(d) Clinical Protocol
Page 89
LY3009104
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
GBD
Global Burden of Disease 
GCP
good clinical practice
GGT
gamma-glutamyltransferase
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

I4V-MC-JAIR(d) Clinical Protocol
Page 90
LY3009104
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
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 
LTE
Long-term Extension
MACE
major adverse cardiovascular events
MCMC
Markov chain Monte Carlo method
MCS
mental component score
MedDRA
Medical Dictionary for Regulatory Activities
MHC
major histocompatibility complex
mFAS
modified full analysis set
MI
multiple imputation
mLOCF
modified last observation carried forward

I4V-MC-JAIR(d) Clinical Protocol
Page 91
LY3009104
MMRM
mixed-effects model of repeated measures
mRNA
messenger RNA
NRI
nonresponder imputation
PCS
physical component score
PD
pharmacodynamics(s)
PE
pulmonary embolism
PK
pharmacokinetic
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
QD
once daily administration
RA
rheumatoid arthritis
RBC
red blood cell
RNA
ribonucleic acid
SAE
serious adverse event
SALT
Severity of Alopecia Tool
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-36 Health Survey
SOA
Schedule of Activities
STAT
signal transducer and activator of transcription
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis

I4V-MC-JAIR(d) Clinical Protocol
Page 92
LY3009104
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

I4V-MC-JAIR(d) Clinical Protocol
Page 93
LY3009104
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
Serum immunoglobulin (IgE)
Low-density lipoprotein
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 94
LY3009104
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 95
LY3009104
Appendix 3.
Study Governance Considerations
Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1. Informed Consent
The investigator is responsible for:

ensuring that the patient understands the nature of the study, the potential risks 
and benefits of participating in the study, and that their participation is voluntary.

ensuring that informed consent is given by each patient or legal representative.  
This includes obtaining the appropriate signatures and dates on the informed 
consent form (ICF) prior to the performance of any protocol procedures and prior 
to the administration of investigational product.

answering any questions the patient may have throughout the study and sharing in 
a timely manner any new information that may be relevant to the patient’s 
willingness to continue his/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

I4V-MC-JAIR(d) Clinical Protocol
Page 96
LY3009104

informed consent form 

other relevant documents (eg, curricula vitae, advertisements)
Appendix 3.1.4. Regulatory Considerations
This study will be conducted in accordance with the protocol and with the:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 97
LY3009104

sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the case report 
forms (CRFs), and study procedures.

make periodic visits to the study site.

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.

I4V-MC-JAIR(d) Clinical Protocol
Page 98
LY3009104
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. 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 3.3.2. Discontinuation of the Study
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP.
Appendix 3.4.
Publication Policy
The publication policy for Study I4V-MC-JAIR is described in the Clinical Trial Agreement.

I4V-MC-JAIR(d) Clinical Protocol
Page 99
LY3009104
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, 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 100
LY3009104
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 8.1.2
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%).

I4V-MC-JAIR(d) Clinical Protocol
Page 101
LY3009104
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.  

I4V-MC-JAIR(d) Clinical Protocol
Page 102
LY3009104
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:  
Analysis 
Seed Value
Proportion of patients achieving SALT score ≤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 a ≥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 a ≥2-point 
improvement from Baseline at Week 36 (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.  

I4V-MC-JAIR(d) Clinical Protocol
Page 103
LY3009104
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 time point 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 time 
point 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 

I4V-MC-JAIR(d) Clinical Protocol
Page 104
LY3009104
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
Abbreviation:  SALT = Severity of Alopecia Tool.
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 1 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 JAIR.2). The testing 
process continues as long as there is at least 1 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. 

I4V-MC-JAIR(d) Clinical Protocol
Page 105
LY3009104
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.

I4V-MC-JAIR(d) Clinical Protocol
Page 106
LY3009104
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 Ethical Review Boards (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 investigational product (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

I4V-MC-JAIR(d) Clinical Protocol
Page 107
LY3009104

alternate delivery of study intervention and ancillary supplies, and

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 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 
downtitration 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:

Patient-reported outcome (PRO) Scalp, Severity of Alopecia Tool (SALT) score, and 
clinician-reported outcomes (ClinROs) for Eyebrows/Eyelashes if visual assessment 
by telemedicine is possible. If NO visual assessment AND ONLY verbal assessment 
by telephone is possible, SALT score, ClinROs for Eyebrows/Eyelashes and Nails, 
and PROs for Eye Irritation should not be assessed.

AEs and product complaints.

Concomitant medications.

Columbia Suicide Severity Rating Scale (C-SSRS) (Since Last Visit Version), 
Self-Harm Supplement Form, and Self-Harm Form.
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 108
LY3009104
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 test when 
applicable, as per the study protocol schedule of activities.

A urine pregnancy test should be sent to female patients of childbearing 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 a 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, and

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 ERB 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.

I4V-MC-JAIR(d) Clinical Protocol
Page 109
LY3009104
4. Adjustments to Visit Windows 
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 per the visit window 
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, visits 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. 

I4V-MC-JAIR(d) Clinical Protocol
Page 110
LY3009104
Appendix 9.
Protocol Amendment I4V-MC-JAIR(d) 
Summary A Multicenter, Randomized, Double-Blind, 
Placebo-Controlled, Phase 3 Study to Evaluate the 
Efficacy and Safety of Baricitinib in Adult Patients with 
Severe or Very Severe Alopecia Areata (BRAVE-AA2)
Overview
Protocol I4V-MC-JAIR (A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 
Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients with Severe or 
Very Severe Alopecia Areata [BRAVE-AA2]) has been amended.  The new protocol is indicated 
by amendment (d) 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
correct typographical errors, and
clarify study procedures.
The overall changes and rationale for the changes made to this protocol are described in the 
following table.

I4V-MC-JAIR(d) Clinical Protocol
Page 111
LY3009104
Amendment Summary for Protocol I4V-MC-JAIR Amendment (d)
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 time point 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 to Other Secondary Endpoints 
to key Secondary Endpoints

Moved ClinROs for EB and EL to Key Secondary Endpoints at Week 36 from Other 
Secondary ” 

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) to 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

Clarified Mean change from Baseline in HADS total score at Weeks 24 and 36 to specify 
HADS-A and HADS-D

Added clarifying statement in regard to the potential for additional database locks and 
Interim Analysis

Updated key 
secondary 
endpoints to reflect 
the analysis that
will be conducted

Removed SALT score percentages for severe or very severe AA 

Updated language regarding interim analysis in Statistical Analysis 

Clarification per 
regulatory feedback

For flexibility

Removed baseline testing for Fisher exact test

Error correction
Section 2:  Schedule of Activities 

Added leading statement regarding addition of Appendix 8, which addresses provisions in 
study conduct under exceptional circumstances

Clarification

Corrected error introduced in last amendment.  Hamilton-Norwood Scale – changed Week 
56 collection to Week 52

Error correction

Corrected error introduced in last amendment – hematology to be collected at Week 8

Error correction

I4V-MC-JAIR(d) Clinical Protocol
Page 112
LY3009104
Section # and Name
Description of Change
Brief Rationale
Section 3.3:  Benefit/Risk Assessment

Corrected incomplete sentence at the end of the first paragraph

Error correction
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 patient achieving a SALT90 to Other Secondary 
Endpoints

Changed time point 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 to Other Secondary Endpoints 
to key Secondary Endpoints

Moved ClinROs for EB and EL to Key Secondary Endpoints at Week 36 from Other 
Secondary ”

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) to 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

Clarified Mean change from Baseline in HADS total score at Weeks 24 and 36 to specify 
HADS-A and HADS-D

Added clarifying statement in regard to the potential for additional database locks and 
Interim Analysis

Clarification
Section 5.1:  Overall Design

Removed wording referring to AA severity to improve clarity of stratification

Clarification per 
regulatory feedback
Section 6.1:  Inclusion Criteria

Updated pregnancy language for Inclusion Criterion [5a]

Clarification
Section 7.2:  Method of Treatment
  Assignment

Removed SALT score percentages for severe or very severe AA to improve clarity of 
stratification

Corrected information on visit and week for IP assignment by IWRS

Clarification per 
regulatory feedback

Error correction
Section 9.1.1.1:  Severity of
  Alopecia Tool

Added “(SALT) Score” to section heading

Error correction
Section 9.4.4:  Laboratory Tests

Clarified that home visits to collect blood and urine samples may be permitted under normal 
protocol operations

For flexibility of
study conduct
Section 10.3.1:  General Statistical 

Updated language regarding interim analyses being conducted

For flexibility 

I4V-MC-JAIR(d) Clinical Protocol
Page 113
LY3009104
Section # and Name
Description of Change
Brief Rationale
 Considerations
Section 10.3.1.1. Analysis Methods 

95% CI will also be reported changed to may be reported

Error
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 JAIR.2)

Updated Key Secondary Null Hypotheses to reflect updates to Key Secondary Objectives

Updated based on 
revisions to key 
secondary 
endpoints
Section 10.3.3.1:  Primary Analyses

Added language to clarify missing data imputation for data collected during remote visits

Added language to clarify what data may be included in additional analysis

Clarification of 
analyses 
description per
regulatory feedback
Section 10.3.3.2:  Secondary Analyses

Added statement that additional analysis of the secondary efficacy outcome may be 
performed

Clarification of 
analysis description 
per regulatory 
feedback
Section 10.3.4:  Safety Analyses

Updated wording to clarify data included in the safety analysis

Clarification
Section 10.3.5.1. Subgroup Analyses

Added baseline value wording to logistic model

For Clarity 
Section 10.3.6.3:  Week 36 Primary
  Outcomes Analyses and Other Interim
  Analyses

Added wording to state that interim analysis will be described in the SAP

Clarification
Appendix 6.1.1:  Placebo Multiple
  Imputation

Sentence added stating that a Markov chain Monte Carlo method will be used

Adjusted analysis table to reflect planned analysis
   Removed statement about mLOCF

Clarification
Appendix 8:  Provisions for Changes in
Study Conduct During Exceptional
Circumstances

Added Appendix 8, Provisions for Changes in Study Conduct During Exceptional 
Circumstances

To enable 
continued conduct 
of the study using 
remote visits
Abbreviations: AA = alopecia areata; ClinRO = clinician-reported outcome; EB = eyebrow; EL = eyelash; IP = investigational product; IWRS = interactive web-
response system; mLOCF = modified last observation carried forward; PRO = patient-reported outcome; SALT50 = at least 50% improvement from Baseline 
in Severity of Alopecia Tool score; SAP = statistical analysis plan.

Leo Document ID = a20c70c5-7cc5-4fc3-b70d-468f9514e75b
Approver: 
Approval Date & Time: 02-Nov-2020 19:28:21 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 02-Nov-2020 21:01:24 GMT
Signature meaning: Approved
PPD
PPD