A Phase 2 Study to Evaluate the Efficacy and Safety of LY3462817 in Participants With Moderately to Severely Active Rheumatoid Arthritis
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Sponsor: Eli Lilly and Company

Protocol: J1A-MC-KDAD(b)
Phase 2 Study to Evaluate the Efficacy and Safety of LY3462817 in Participants With 
Moderately to Severely Active Rheumatoid Arthritis
NCT04634253
Approval Date: 11-Dec-2020

C O N FI D E N TI A L
Pr ot oc ol  n u mber J 1 A -M C -K D A D( b)
1
Title P a ge
C o nfi d e nti al I nf or m ati o n
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al a n d i s i nt e n d e d f or t h e u s e of cli ni c al i n v e sti g at or s.  It i s t h e pr o p ert y of 
Eli Lill y a n d C o m p a n y or it s s u b si di ari e s a n d s h o ul d n ot b e c o pi e d b y or di stri b ut e d t o p er s o n s n ot i n v ol v e d i n t h e cli ni c al 
i n v e sti g ati o n of L Y 3 4 6 2 8 1 7 , u nl e s s s u c h p er s o n s ar e b o u n d b y a c o nfi d e nti alit y a gr e e m e nt wit h Eli Lill y a n d C o m p a n y or it s 
s u b si di ari e s. 
N ot e t o R e g ul at or y A ut h oriti e s:   T hi s d o c u m e nt m a y c o nt ai n pr ot e ct e d p er s o n al d at a a n d/ or c o m m er ci all y c o nfi d e n ti al 
i nfor m ati o n e x e m pt fr o m p u bli c di s cl o s ur e.  Eli Lill y a n d C o m p a n y r e q u e st s c o n s ult ati o n r e g ar di n g r el e a s e/r e d a cti o n pri or t o a n y 
p u bli c r el e a s e.  I n t h e U nit e d St at e s, t hi s d o c u m e nt i s s u bj e ct t o Fr e e d o m of I nf or m ati o n A ct ( F OI A) E x e m pti o n 4 a n d m a y n ot b e 
r epr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e writt e n a p pr o v al of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s .
Pr ot oc ol Title: A P hase 2 St u d y  t o E valuate t he Efficac y  a n d Safety of  L Y 3 4 6 2 8 1 7 i n 
P articip a nts wi t h M o deratel y t o Se verel y Acti ve R he u mat oid Art hri tis
Pr ot oc ol N u m ber: J 1 A-M C -K D A D
A me n d me nt N u m ber: ( b)
C o m p o u n d : L Y 3 4 6 2 8 1 7
St u d y P h ase: P hase 2
S h ort Title: A P hase 2 St u d y  t o E valuate t he Efficac y  a n d Safety of  L Y 3 4 6 2 8 1 7 i n Parti ci pa nts
wi t h M o deratel y t o Se verel y Act i ve R he u mat oi d Art hritis
Acr o n y m : K D A D
S p o ns or N a me: El i Lill y  a n d C o mpa n y
Le g al Re gistere d A d dress: I n dia na p olis, I n dia na, U S A 4 6 2 8 5
Re g ul at or y A ge nc y I de ntifier N u m ber(s)
I N D: 1 5 0 7 1 0
E u dra C T n u m ber: 2 0 2 0 ‐ 0 0 2 6 7 3‐ 1 0
A p pr o v al D ate: Pr ot oc ol A me n d me nt ( b ) Electr o nicall y Si g ne d a n d A p pr o ve d b y Lill y o n date 
pr o vi de d bel o w.
A p pr o v al D at e: 1 1- D e c- 2 0 2 0 G M T

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Protocol number J1A-MC-KDAD(b)
2
Medical Monitor Name and Contact Information will be provided separately.

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Protocol number J1A-MC-KDAD(b)
3
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
KDAD Amendment (a)
21-Sep-2020
Original Protocol 
05-Aug-2020
Amendment [b] 
This amendment occurred before any study participant was consented or dosed at any study site 
in Europe.
Overall Rationale for the Amendment:
The purpose of this protocol amendment is to clarify study procedures and statistical 
considerations in response to European regulatory agency feedback.
Section # and Name
Description of Change
Brief Rationale
Section 6.3. Measures to Minimize Bias: 
Randomization and Blinding
Section 7.1.2. Criteria for Permanent 
Discontinuation of Study Intervention
Section 8.2.6. Tuberculosis Testing and 
Monitoring
Removed medical monitoring 
wording
Clarification 
Section 7.1.1. Criteria for Temporary 
Interruption (Withholding) of Study 
Intervention
Section 7.1.1.1. Infection-related Criteria 
for Temporary Withholding of Study 
Intervention 
Section 7.2.1. Discontinuation of 
Inadvertently Enrolled Participants 
Modified medical monitoring 
wording
Clarification
Section 9.2. Sample Size Determination

DAS28-CRP change 
from baseline explained 

MMRM analysis 
information added
Clarification
Section 9.4.1. General Considerations
Clarified adjustments for 
multiplicity 
Clarification
Section 9.5. Interim Analyses
Provided additional clarification 
on interim analysis
Clarification

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Protocol number J1A-MC-KDAD(b)
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Table of Contents
1.
Protocol Summary......................................................................................................7
1.1.
Synopsis.......................................................................................................................7
1.2.
Schema.......................................................................................................................10
1.3.
Schedule of Activities (SoA) ......................................................................................11
2.
Introduction..............................................................................................................18
2.1.
Study Rationale ..........................................................................................................18
2.2.
Background ................................................................................................................18
2.3.
Benefit/Risk Assessment ............................................................................................20
3.
Objectives and Endpoints.........................................................................................21
4.
Study Design .............................................................................................................23
4.1.
Overall Design............................................................................................................23
4.2.
Scientific Rationale for Study Design .........................................................................23
4.3.
Justification for Dose..................................................................................................24
4.4.
End of Study Definition..............................................................................................25
5.
Study Population ......................................................................................................26
5.1.
Inclusion Criteria........................................................................................................26
5.2.
Exclusion Criteria.......................................................................................................28
5.3.
Lifestyle Considerations .............................................................................................31
5.4.
Screen Failures...........................................................................................................31
6.
Study Intervention....................................................................................................32
6.1.
Study Intervention(s) Administered ............................................................................32
6.2.
Preparation/Handling/Storage/Accountability.............................................................33
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................33
6.4.
Study Intervention Compliance...................................................................................34
6.5.
Concomitant Therapy .................................................................................................34
6.5.1.
Permitted Rheumatoid Arthritis Concomitant Therapy................................................34
6.5.2.
Prohibited Concomitant Therapy ................................................................................35
6.5.3.
Standard of Care Therapy after Week 14 ....................................................................35
6.6.
Dose Modification......................................................................................................36
6.7.
Intervention after the End of the Study........................................................................36
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................37
7.1.
Discontinuation of Study Intervention ........................................................................37
7.1.1.
Criteria for Temporary Interruption (Withholding) of Study 
Intervention ................................................................................................................37
7.1.2.
Criteria for Permanent Discontinuation of Study Intervention.....................................38
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................39
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................40
7.3.
Lost to Follow up .......................................................................................................40
8.
Study Assessments and Procedures .........................................................................41
8.1.
Efficacy Assessments .................................................................................................41

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Protocol number J1A-MC-KDAD(b)
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8.1.1.
Disease Activity Score–High-Sensitivity C-Reactive Protein 
(DAS28-hsCRP).........................................................................................................41
8.1.2.
Disease Activity Score–Erythrocyte Sedimentation Rate 
(DAS28-ESR).............................................................................................................41
8.1.3.
American College of Rheumatology Criteria (ACR20, ACR50, 
and ACR70) ...............................................................................................................42
8.1.4.
Tender Joint Count and Swollen Joint Count ..............................................................42
8.1.5.
Physician’s Global Assessment of Disease Activity 
(PhGADA_VAS)........................................................................................................42
8.1.6.
Patient’s Global Assessment of Arthritis Pain (Visual Analog 
Scale) .........................................................................................................................42
8.1.7.
Patient’s Global Assessment of Disease Activity 
(PaGADA_VAS)........................................................................................................43
8.1.8.
Health Assessment Questionnaire - Disability Index (HAQ-DI)..................................43
8.1.9.
Simplified Disease Activity Index (SDAI)..................................................................43
8.1.10.
Clinical Disease Activity Index (CDAI)......................................................................44
8.1.11.
Medical Outcomes Study 36-Item Short Form Health Survey.....................................44
8.1.12.
MRI Imaging and Synovitis Score ..............................................................................44
8.2.
Safety Assessments ....................................................................................................45
8.2.1.
Physical Examinations................................................................................................45
8.2.2.
Vital Signs..................................................................................................................45
8.2.3.
Electrocardiograms.....................................................................................................45
8.2.4.
Clinical Safety Laboratory Assessments .....................................................................45
8.2.5.
Suicidal Ideation and Behavior Risk Monitoring.........................................................46
8.2.6.
Tuberculosis Testing and Monitoring..........................................................................47
8.2.7.
Hepatitis B Testing and Monitoring ............................................................................48
8.2.8.
Hepatitis C Testing and Monitoring ............................................................................49
8.3.
Adverse Events and Serious Adverse Events ..............................................................49
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................49
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................50
8.3.3.
Follow-up of AEs and SAEs.......................................................................................50
8.3.4.
Regulatory Reporting Requirements for SAEs............................................................50
8.3.5.
Pregnancy...................................................................................................................50
8.3.6.
Adverse Events of Special Interest..............................................................................51
8.3.7.
Product Complaints ....................................................................................................52
8.4.
Treatment of Overdose ...............................................................................................52
8.5.
Pharmacokinetics........................................................................................................53
8.6.
Pharmacodynamics.....................................................................................................53
8.7.
Genetics .....................................................................................................................53
8.8.
Biomarkers.................................................................................................................53
8.9.
Immunogenicity Assessments.....................................................................................54
8.10.
Health Economics.......................................................................................................54
9.
Statistical Considerations.........................................................................................55
9.1.
Statistical Hypotheses.................................................................................................55
9.2.
Sample Size Determination.........................................................................................55

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Protocol number J1A-MC-KDAD(b)
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9.3.
Populations for Analyses ............................................................................................55
9.4.
Statistical Analyses.....................................................................................................56
9.4.1.
General Considerations...............................................................................................56
9.4.2.
Primary Endpoint(s) ...................................................................................................58
9.4.3.
Secondary Endpoint(s)................................................................................................58
9.4.4.
Exploratory Endpoint(s)..............................................................................................59
9.4.5.
Pharmacokinetic/Pharmacodynamic Analyses ............................................................59
9.4.6.
Evaluation of Immunogenicity....................................................................................59
9.4.7.
Other Safety Analyses ................................................................................................60
9.4.8.
Other Analyse(s).........................................................................................................61
9.5.
Interim Analyses.........................................................................................................61
9.6.
Data Monitoring Committee (DMC)...........................................................................62
10.
Supporting Documentation and Operational Considerations ................................63
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................63
10.1.1.
Regulatory and Ethical Considerations........................................................................63
10.1.2.
Financial Disclosure ...................................................................................................63
10.1.3.
Informed Consent Process ..........................................................................................64
10.1.4.
Data Protection...........................................................................................................64
10.1.5.
Committees Structure .................................................................................................64
10.1.6.
Dissemination of Clinical Study Data .........................................................................65
10.1.7.
Data Quality Assurance ..............................................................................................65
10.1.8.
Source Documents......................................................................................................66
10.1.9.
Study and Site Start and Closure.................................................................................66
10.1.10. Publication Policy.......................................................................................................67
10.1.11. Investigator Information .............................................................................................67
10.1.12. Long-Term Sample Retention.....................................................................................67
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................68
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.......................................................71
10.3.1.
Definition of AE.........................................................................................................71
10.3.2.
Definition of SAE.......................................................................................................72
10.3.3.
Recording and Follow-Up of AE and/or SAE .............................................................73
10.3.4.
Reporting of SAEs......................................................................................................74
10.4.
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...............................................................................................76
10.5.
Appendix 5: Genetics .................................................................................................80
10.6.
Appendix 6:  Recommended Laboratory Testing for 
Hypersensitivity Events..............................................................................................81
10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up 
Assessments ...............................................................................................................83
10.8.
Appendix 8: Provisions for Changes in Study Conduct During 
Exceptional Circumstances.........................................................................................86
10.9.
Appendix 9: Abbreviations .........................................................................................89
10.10.
Appendix 10:  Country Specific Requirements ...........................................................95
11.
References.................................................................................................................96

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Protocol number J1A-MC-KDAD(b)
7
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Phase 2 Study to Evaluate the Efficacy and Safety of LY3462817 in 
Participants with Moderately to Severely Active Rheumatoid Arthritis
Short Title: A Phase 2 Study to Evaluate the Efficacy and Safety of LY3462817 in Participants 
with Moderately to Severely Active Rheumatoid Arthritis
Rationale:
Rheumatoid arthritis (RA) is a common, systemic autoimmune inflammatory disease, 
characterized by synovial inflammation leading to pain, swelling, stiffness, and progressive 
destruction and deformity of small and large joints. Current treatment of RA prioritizes timely 
initiation and modification of disease-modifying antirheumatic drug (DMARD) therapy to bring 
patients to a target of sustained low disease activity (LDA) or remission. Patients typically begin 
treatment with oral conventional synthetic DMARDs (csDMARDs); but if the treatment target is 
not achieved, they receive additional therapy with biologic DMARDs (bDMARDs) or targeted 
synthetic DMARDs (tsDMARDs). However, 20 to 30% of patients with RA remain refractory to 
current therapies. There is a need for new, effective treatment options in these patients.
LY3462817 is a humanized immunoglobulin (Ig) G1 monoclonal antibody that binds to and is an 
agonist to human programmed cell death protein 1 (PD-1). LY3462817 binding to PD-1 is 
expected to stimulate the physiological immune inhibitory pathway to restore immune 
regulation; this constitutes a novel approach to treat patients with autoimmune or 
auto-inflammatory diseases.
This study aims to evaluate the efficacy of LY3462817 in adult participants with moderately to 
severely active RA who have had an inadequate response to either csDMARD or to 
bDMARDs/tsDMARDS.  
Objectives and Endpoints
Objectives
Endpoints and Estimands
Comparison Groups: Placebo vs LY3462817
[time frame for endpoint evaluation: 12 weeks from randomization, unless stated otherwise]
Primary
To evaluate the efficacy of LY3462817 in adult 
participants with moderately to severely active 
RA
Change from baseline in DAS28-CRP.
The primary comparison will be assessed using a 
hypothetical efficacy estimand strategy to address the 
intercurrent event of early discontinuation where the mean 
change from baseline will be evaluated using only data up 
until discontinuation as if all subjects remained on 

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Protocol number J1A-MC-KDAD(b)
8
randomized treatment.
Secondary
To describe the safety and tolerability of 
LY3462817 compared to placebo

Safety assessments such as AEs, SAEs
To evaluate the effect of LY3462817 on 
measures of disease activity 

Proportion of participants achieving ACR20, ACR50, 
and ACR70

Change from baseline for physician-assessed 
individual components:
o
68 tender joint count
o
66 swollen joint count
o
physician’s global assessment of disease activity 
(VAS)

Change from baseline for mean SDAI

Change from baseline for mean CDAI
To describe the effect of LY3462817 on PROs 
Change from baseline for:

Individual components of the ACR core set:
o
patient’s global assessment of disease activity 
(VAS),
o
patient’s global assessment of arthritis pain 
(VAS), and 
o
patient’s assessment of physical function 
(HAQ-DI)

SF-36
To characterize the pharmacokinetics of 
LY3462817
Observed drug concentration 
Abbreviations: ACR = American College of Rheumatology; ACR20 = 20% improvement in American College of 
Rheumatology criteria; ACR50 = 50% improvement in American College of Rheumatology criteria; 
ACR70 = 70% improvement in American College of Rheumatology criteria; AE = adverse event; 
CDAI = Clinical Disease Activity Index; CRP = C-reactive protein; DAS28 = Disease Activity Score modified to
include the 28 diarthrodial joint count; HAQ-DI = Health Assessment Questionnaire-Disability Index; 
PRO = patient-reported outcome; RA = rheumatoid arthritis; SAE = serious adverse event; SDAI = Simplified 
Disease Activity Index; SF-36 = Study 36-Item Short Form Health Survey; VAS = visual analog scale.
Overall Design
This is a Phase 2, proof-of-concept, placebo-controlled, double-blind, randomized study in adult 
participants with moderately to severely active RA who have had an inadequate response to 
csDMARDs, or to bDMARDs/tsDMARDs. Participants will be administered LY3462817 or 
placebo intravenously (IV) once every 4 weeks (Q4W).

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Protocol number J1A-MC-KDAD(b)
9
Screening Period (Visit 1, Days -42 to -1)
Participants will sign the informed consent document(s) at Visit 1, prior to completion of any 
procedures. Participants will be evaluated for study eligibility ≤42 days prior to the baseline visit 
(Visit 2).  
Period 1: Double-blind Treatment (Visits 2 to 6; 12 weeks)
At the baseline visit (Visit 2), participants who fulfill the eligibility criteria will be randomized to 
receive LY3462817 700 mg, LY3462817 300 mg, or placebo in an allocation ratio of 2:1:1.
The double-blind treatment period will establish the clinical efficacy and safety of LY3462817. 
The study will be evaluated for the primary objective at the end of the double-blind treatment 
period.
Period 2 (Visits 6 to 10; 12 weeks)
In Period 2, participants assigned to LY3462817 at baseline, and achieving low disease activity 
(CDAI ≤10) at Week 14 will continue to receive LY3462817 to assess safety and tolerability 
data and evaluate clinical activity with additional dosing. All other participants at Week 14, 
regardless of baseline treatment assignment, will receive standard of care treatment at the 
investigator’s discretion.  
Post-treatment Safety Follow-up Period (Visits V801 and 802; 12 weeks)
Following Period 2, participants will be followed posttreatment for 12 weeks to assess safety, 
study drug exposure, and clinical disease activity.  
Disclosure Statement: This is a parallel, 3-arm treatment study that is participant-blinded and 
investigator-blinded.
Number of Participants:
Approximately 80 participants will be randomly assigned to study intervention. At the 
completion of the study, approximately 40 participants will have been randomized to 
LY3462817 700 mg and 20 participants will have been randomized to LY3462817 300 mg and 
placebo during the double-blind treatment.
Intervention Groups and Duration:
Participants will receive 1 of the following study interventions: intravenous LY3462817 300 mg, 
700 mg, or placebo every 4 weeks for 12 weeks. Participants assigned to LY3462817 at baseline, 
and achieving low disease activity (CDAI ≤10) at Week 14 will continue to receive LY3462817 
through Week 24.  
Data Monitoring Committee: No data monitoring committee, but there will be an internal 
assessment committee.

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Protocol number J1A-MC-KDAD(b)
10
1.2.
Schema
Notes:
For details about the study intervention doses, see Section 6.1.
Diagonal dashed arrows indicate transition to SOC therapy at Week 14. For details about SOC therapy, see 
Section 6.5.3.  
Abbreviations: Pbo = placebo; LDA = Low Disease Activity; LY = LY3462817; mg = milligrams; Q4W = once 
every 4 weeks; SOC = Standard of Care; V = visit; W = week. 

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Protocol number J1A-MC-KDAD(b)
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1.3.
Schedule of Activities (SoA)
The SoA should be followed for all participants enrolled in Study KDAD. If participation in this study is affected by exceptional 
circumstances, such as a pandemic or natural disaster, please refer to Section 10.8, Appendix 8, for additional guidance.
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Informed Consent
X
Written informed consent must be 
obtained before any study procedures or 
assessments.
Inclusion and exclusion 
criteria, review and 
confirm
X
X
Demographics
X
Preexisting conditions 
and medical history, 
including relevant 
surgical history
X
Prespecified medical 
history (indication and 
history of interest)
X
Substance use (alcohol, 
caffeine, tobacco use)
X
X
Prior treatments for RA
X
Any previous therapy for RA in the past 
15 years that has now been 
discontinued.

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Protocol number J1A-MC-KDAD(b)
12
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
For concomitant medications of interest 
(such as background therapies),
additional data are collected.
Adverse events (AEs)
X
X
X
X
X
X
X
X
X
X
X
X
X
AE collection begins when ICF is 
signed (Section 10.3). For AESIs, 
additional data are collected 
(Section 8.3.6).
Participant-Reported Outcomes (Electronic)
Patient’s Global 
Assessment of Arthritis 
Pain (VAS) 
X
X
X
X
X
X
X
X
X
X
X
X
X
Administer before any clinical 
assessments and dosing
Health Assessment 
Questionnaire-
Disability Index (HAQ-
DI)
X
X
X
X
X
X
X
X
X
X
X
X
X
Administer before any clinical 
assessments and dosing
Patient's Global 
Assessment of Disease 
Activity 
(PaGADA_VAS)
X
X
X
X
X
X
X
X
X
X
X
X
X
Administer before any clinical 
assessments and dosing
Medical Outcomes 
Study 36-Item Short 
Form Health Survey 
(SF-36 v2, Acute)
X
X
X
X
X
Administer before any clinical 
assessments and dosing

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
13
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Physical Evaluation
Height
X
Weight
X
X
X
X
Vital Signs (BP, PR, T)
X
X
X
X
X
X
X
X
X
X
X
X
X
Supine or sitting blood pressure and PRs
obtained at approximately same time as 
the ECG, prior to blood sampling.
Complete physical 
examination
X
X
X
Excludes pelvic, rectal, and breast 
examinations.
Symptom-directed 
physical examination
X
X
X
X
X
X
X
X
X
X
Performed at the discretion of the 
investigator. Assess prior to dosing.
12-lead ECG (local)
X
X
X
X
Participants to be supine for at least 
5 minutes before ECG and remain 
supine but awake during ECG. Assess 
prior to blood sampling.
Chest x-ray 
(posterior-anterior and 
lateral view; local)
X
Documentation of radiologic 
reports/films taken within 3 months 
prior to screening is acceptable. Lateral 
view is optional or according to local 
guidelines.
MRI (Hand/Wrist)
X
X
Performed only after the all eligibility 
criteria are met except: criterion 6. 
Evaluate the same hand/wrist at 
screening and Week 12 prior to dosing.

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
14
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Health Care Professional RA Assessments (Electronic)
Clinician-Administered 
Tender/Swollen Joint 
Count (TSJC) (68/66)
X
X
X
X
X
X
X
X
X
X
X
X
X
Collected via an electronic tablet device. 
These joint counts will be performed by 
the Joint Assessor (Section 6.3). 
Determine prior to dosing
Physician's Global 
Assessment of Disease 
Activity 
(PhGADA_VAS)
X
X
X
X
X
X
X
X
X
X
X
X
X
Determine prior to dosing
Clinician-Administered Assessments (Paper)
C-SSRS 
Screening/Baseline
X
Administer before any clinical 
assessments and dosing
C-SSRS Since Last 
Assessed
X
X
X
X
X
X
X
X
X
X
X
X
Administer before any clinical 
assessments and dosing
Self-harm Supplement 
Form
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-Up 
Form
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Tests and Sample Collections
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
Collect prior to dosing
Clinical Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
In addition to scheduled assessments, 
these laboratory tests may also be 
performed as clinically indicated.
Collect prior to dosing.

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
15
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Urinalysis
X
X
X
X
X
X
X
In addition to scheduled assessments, 
these laboratory tests may also be 
performed as clinically indicated.
Collect prior to dosing.
Serum pregnancy
X
For all women of childbearing potential 
(Section 10.4).
Urine pregnancy
(local)
X
X
X
X
X
X
X
X
X
X
Determine results prior to dosing
Follicle Stimulating 
Hormone (FSH)
X
For women who are considered 
postmenopausal to confirm 
postmenopausal status.
C-Reactive Protein, 
high-sensitivity 
(hsCRP)
X
X
X
X
X
X
X
X
X
X
X
X
X
Collect prior to dosing
Erythrocyte 
sedimentation rate 
(ESR)
X
X
X
X
X
X
X
Collect prior to dosing
Rheumatoid factor (RF)
X
X
X
X
X
X
X
Collect prior to dosing
Anticyclic citrullinated 
peptide (anti-CCP)
X
X
X
X
X
X
X
Collect prior to dosing
Soluble PD-1
X
X
X
X
X
X
X
X
X
X
Collect prior to dosing
Soluble PD-L1
X
X
X
X
X
X
X
X
X
X
Collect prior to dosing.

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
16
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Tuberculosis (TB) test
X
See Section 8.2.7 for details of TB 
testing. Participants will return 48 to 
72 hours after a tuberculin test (TST) for 
their test results. If the QuantiFERON®-
TB Gold test or T-SPOT® TB test is 
available, either test may be used 
instead of the PPD TB test. The 
QuantiFERON®-TB test is done 
centrally or locally; the T-SPOT® TB 
test must be done locally.
Human 
immunodeficiency 
virus (HIV) screening 
tests
X
Hepatitis C virus 
(HCV) screening tests
X
Hepatitis B virus 
(HBV) screening tests
X
Includes HBsAg and anti-HBc.
Hepatitis B virus 
(HBV) DNA
X
X
X
X
X
Any enrolled participant who is 
HBcAb+ will undergo monitoring of 
HBV DNA during the study treatment.
Flow cytometry panel
X
X
X
X
X
X
X
Includes: TBNK, collect prior to dosing
Cytokine panel
X
X
X
X
X
X
X
Collect prior to dosing

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
17
Study 
J1A-MC-KDAD
Screen
Period 1: Double-blind treatment
Period 2
ED
Post-treatment 
follow-up
Comments
Day ± Visit Tolerance
-42
to -1
1
14
± 7
28
± 7
56
± 7
84
± 7
98
± 7
112
± 7
140
± 7
168
± 7
Any
196
± 7
252
± 7
Visit 1 procedures may be conducted 
over more than 1 day as long as all tasks 
are completed within the tolerance 
window.
Week
-
2
4
8
12
14
16
20
24
-
28
36 or
ETV 
+ 12
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
ET
V801
V802
Procedures
Immunoglobulin panel
X
X
X
X
X
Includes: IgG, IgM, and IgA
Collect prior to dosing
Pharmacokinetic 
samples
X
X
X
X
X
X
X
X
X
X
Collect prior to dosing
Immunogenicity 
samples
X
X
X
X
X
X
X
X
Collect prior to dosing
Receptor occupancy
X
X
X
X
X
X
X
X
X
Collect prior to dosing
Peripheral helper 
T cells
X
X
X
X
X
X
X
X
X
Collect prior to dosing
Stored samples
Genetics sample
X
Collect prior to dosing
Exploratory biomarker 
samples
X
X
X
X
X
X
X
X
X
X
See Section 10.2 for details
Collect prior to dosing
Randomization and dosing
Randomization
X
Administer study drug
X
X
X
X
X
X
X
During Weeks 16 - 24 administer study 
drug only if participant achieved low 
disease activity at Week 14.
Abbreviations: AESI = adverse event of special interest; anti-HBc = hepatitis B core antibody; BP = blood pressure; C-SSRS = Columbia-Suicide Severity 
Rating Scale; ECG = electrocardiogram; ED = early discontinuation visit; ET = early termination; ETV = early termination visit; HBcAb+ = hepatitis B core 
antibody positive; HBsAg = hepatitis B surface antigen; ICF = informed consent form; IgA = immunoglobulin A; IgG = immunoglobulin G; 
IgM = immunoglobulin M; MRI = magnetic resonance imaging; PD-1 = programmed cell death protein 1; PD-L1 = programmed cell death ligand 1; 
PPD = purified protein derivative; PR = pulse rate; RA = rheumatoid arthritis; T = temperature; TBNK = T cells, B cells, natural killer cells; V = visit; 
VAS = visual analog scale.

C O N FI D E N TI A L
Pr ot oc ol  n u mber J 1 A -M C -K D A D( b)
1 8
2.
I ntr o d ucti o n
2. 1.
St u d y R ati o n ale
R he u m at oi d art hritis
R he u mat oi d art hrit is ( R A) is a c om m o n, s y ste mic a ut oi m m u ne i nfla m mat or y disease, 
c haracterize d b y s yn o vial i nfla m mat i on lea di n g t o pai n, s welli n g, stiff ness, a n d pr o gressi ve 
destr ucti o n a n d def or mit y of  s mall a n d lar ge j oi nts. Patie nts e x perie nce i m paire d p h ysical 
f u ncti on, s ocial partici pati o n, a n d healt h- relate d q uality of  life. Patie nts als o ha ve i ncrease d ris k 
of  sig nifica nt n o n m usc ul o s keletal c o mor bi di ties ( M utr u et al. 1 9 8 5; D ora n et al . 2 0 0 2; Si h v o ne n 
et al. 2 0 0 4; A vi ña-Z u bieta e t al. 2 0 0 8, 2 0 1 2; C h oi et al. 2 0 1 3; Ki m et al. 2 0 1 3; Lee a n d P o pe 
2 0 1 4; Pi cer n o et al. 2 0 1 5; Si m on et al . 2 0 1 5; O g die et al . 2 0 1 8).
C urre nt tre at me nt of R A
C urre nt treat me nt of R A pri oritizes t i mel y i nitiati o n a n d m o dificati on of  disease -m o dif yi n g 
a nt irhe u mat ic dr u gs (D M A R D ) t hera p y t o bri n g patie nts t o a tar get of s ustai ne d l o w disease 
acti vit y ( L D A) or re missi o n ( Si n g h et al. 2 0 1 6; S m ole n et al. 2 0 2 0 ). Ac hie ve me nt of t hese 
tar gets i m pr o ves s h ort- a n d l o n g -t er m patient  healt h o ut c o m es, i ncl u di n g pre ve nt i on of 
pr o gressi ve, irre versi ble str uct ural j o i nt d a ma ge ( Mai ni et al. 2 0 0 4; S mol e n et al. 2 0 2 0). 
T he treat me nt tar get ca n be met i n m ost patie nts wit h t he t hera pe utic o pti o ns c urre nt l y a vaila ble, 
w hic h i ncl u de c o n ve nti o nal s y nthetic D M A R D S ( cs D M A R Ds), bi o l ogi c D M A R Ds 
( b D M A R Ds), a n d tar gete d s y nt hetic D M A R Ds (tsD M A R Ds ). Ho we ver, 2 0 t o 3 0 % of t he 
pati e nts wit h R A re mai n refract or y t o c urre nt t hera pies. F or t hese patient s, ne w treat me nt o pti o ns 
are nee de d ( S mol e n et al. 2 0 2 0).
St u d y K D A D
T his st u d y ai ms t o e val uate t he efficac y of L Y 3 4 6 2 8 1 7 i n a d ult partici pa nts wit h m o deratel y t o 
se verel y acti ve R A w h o ha ve ha d a n i na de q uate res p o nse t o cs D M A R Ds, or t o
b D M A R Ds /tsD M A R Ds.   
2. 2.
B ac k gr o u n d
L Y 3 4 6 2 8 1 7 is a h u ma nize d i m m u n o gl o b uli n (I g) G 1 m o n ocl o nal a nt i b o d y t hat bi n ds t o a n d is a n 
a g o nist t o h u ma n pr o gra m me d cell deat h pr otei n 1 ( P D -1). 
 
 
 
 
 
P D -1 p at h w a y i n a ut oi m m u ne dise ase s
P r o gra m me d cell deat h pr otei n 1 e x pressi o n was f o u n d t o be hi g h a n d pr o gra m me d cell deat h 
li ga n d 1 (P D -L 1 ) ( w hic h bi n ds t o P D-1) e x pressi o n l ow i n t he s y n o vi u m of pat ient s wit h R A
( G u o et al. 2 0 1 8). C haracterizati on of pat h o ge nic, hi g hl y  P D- 1-e x pressi n g T -cell s u bsets wit hi n 
C CI

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
19
the synovium of patients with RA showed them to be uniquely poised to promote B-cell 
responses and antibody production (Rao et al. 2017). Additionally, patients with RA tend to have 
autoantibodies to PD-L1 and increased soluble PD-1 (sPD-1) and PD-L1 (Wan et al. 2006), all of 
which correlate with disease activity.  
Evidence of the PD-1 pathway pathology having a significant role in autoimmune diseases has 
also been demonstrated in psoriasis (Gulati et al. 2015), psoriatic arthritis (Bommarito et al. 
2017), giant cell vasculitis (Zhang et al. 2017), multiple sclerosis (Trabattoni et al. 2009), and 
systemic sclerosis (Fukasawa et al. 2017).
LY3462817
Information on the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of 
LY3462817 comes from the completed study J1A-MC-KDAB (KDAB) and from the ongoing 
study J1A-MC-KDAC (KDAC).
Study
Study design
Population
Study interventions
KDAB
Single ascending dose, first in 
human, Phase 1
Healthy participants
LY3462817: 0.1, 0.4, 2, 8, 30, 120, 350, 
or 700 mg IV
120 mg SC
KDAC
Double-blind, multiple ascending 
dose, placebo-controlled, Phase 1b. 
Participants with 
psoriasis
LY3462817: 75, 300, or 700 mg Q4W IV
for 12 Weeks
Abbreviations: IV = intravenous; Q4W = once every 4 weeks; SC = subcutaneous.
As of 02 September 2020, 47 healthy participants in Study KDAB have received LY3462817. 
Six participants received 75 mg and 7 participants have received 300 mg LY3462817 in Study 
KDAC.
No deaths or serious adverse events (SAEs) were reported so far in these studies, and no 
participants discontinued because of an adverse event (AE). Overall, no clinically significant 
safety concerns were identified with single-dose intravenous (IV) administration of LY3462817 
up to 700 mg and subcutaneous (SC) administration of LY3462817 120 mg. Also, no clinically 
significant safety concerns have been identified with multiple-dose administration of LY3462817 
up to 300 mg in Study KDAC.
The PK of LY3462817 has been evaluated following single doses (Study KDAB) and a small 
subset of the 75 mg multiple dose (Study KDAC) cohort. Nonlinear disposition that is 
characteristic of many monoclonal antibodies was observed at lower doses and the PK was 
approximately dose-proportional at doses equal to and greater than 30 mg. Based on 
noncompartmental analysis, in the dose linear range (≥30 mg), LY3462817 has estimated 
clearance of 10.9 mL/hr, volume of distribution of 3.9 L, and a terminal half-life of 
approximately 10 days. A comparison of exposure from the single dose 120 mg IV and SC 
cohorts indicates a bioavailability of approximately 60%. Across the IV cohorts, the median time 
to reach Cmax ranges between 2 to 8 hours while for 120 mg SC, the median is approximately 9.5 
days. Given the limited PK data in the multiple dose cohort (75 mg IV once every 4 weeks 
[Q4W]), results were not statistically analyzed. Additionally, in Study KDAB, receptor 
occupancy (RO) and sPD-1 concentrations in healthy volunteers following single IV doses of 
LY3462817 were collected and analyzed. Together, both are interpreted as measures of target 
engagement. Across all dose levels tested, RO and sPD-1 increased in both extent and duration 
with increasing dose level.

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
20
In Study KDAC, the 75-mg cohort (N=8) and 300-mg cohort (N=10) were fully enrolled. By the 
data cutoff date, some subjects had received a minimum of 2 doses, while some subjects had 
received a maximum of 4 doses (every-4-week dosing schedule).  
A decision was made to dose escalate to 700 mg on 08 September 2020. Given the overall safety 
profile of LY3462817 to date, the sponsor believes the decision to dose escalate to 700 mg in 
Study KDAC provides sufficient safety data to initiate this study, KDAD. 
A detailed description of the chemistry, pharmacology, toxicology, efficacy, and safety of 
LY3462817 is provided in the Investigator’s Brochure (IB).
2.3.
Benefit/Risk Assessment
Manageable risks associated with most therapeutic monoclonal antibodies are the potential for 
infusion-related hypersensitivity and cytokine release reactions. The infusions in this study will 
be administered at a controlled rate, the study participants will be monitored closely, and 
adjustments in the infusion rate will be made and/or the infusion stopped, if indicated. Additional 
information regarding infusion reaction and hypersensitivity management options is located in 
Section 8.3.6.
No clinically significant safety concerns (including infusion or injection site reactions) were 
observed in Study KDAB, or have been observed in the Study KDAC as of 02 September 2020.
The efficacy of LY3462817 in RA has not been established. Participants may benefit by 
receiving personal health information from the physical examinations and from other routine 
safety assessments performed in this study. 
In summary, in the context of the cumulative knowledge for LY3462817, the benefit/risk balance 
for this study is assessed to be acceptable for testing in Phase 2.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of LY3462817 may be found in the IB. 

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
21
3.
Objectives and Endpoints
Objectives
Endpoints and Estimands
Comparison Groups: Placebo vs LY3462817
[time frame for endpoint evaluation: 12 weeks from randomization, unless stated otherwise]
Primary
To evaluate the efficacy of LY3462817 in adult 
participants with moderately to severely active 
RA
Change from baseline in DAS28-CRP
The primary comparison will be assessed using a 
hypothetical efficacy estimand strategy to address the 
intercurrent event of early discontinuation where the mean 
change from baseline will be evaluated using only data up 
until discontinuation as if all subjects remained on 
randomized treatment.
Secondary
To describe the safety and tolerability of 
LY3462817 compared to placebo
Safety assessments such as AEs, SAEs
To evaluate the effect of LY3462817 on 
measures of disease activity

Proportion of participants achieving ACR20, ACR50, 
and ACR70

Change from baseline for physician-assessed 
individual components:
o
68 tender joint count
o
66 swollen joint count
o
physician’s global assessment of disease activity 
(VAS)

Change from baseline for mean SDAI

Change from baseline for mean CDAI
To describe the effect of LY3462817 on PROs
Change from baseline for:

Individual components of the ACR core set:
o
patient’s global assessment of disease activity 
(VAS),
o
patient’s global assessment of arthritis pain 
(VAS), and 
o
patient’s assessment of physical function (HAQ-
DI)

SF-36

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
22
To characterize the pharmacokinetics of 
LY3462817
Observed drug concentration
Exploratory
To explore the effect of LY3462817 on other 
measures of disease activity

Proportion of participants achieving LDA or remission 
using the following measures: DAS28-CRP, 
DAS28-ESR, SDAI, and CDAI at all time points 
collected  

Change from baseline in the RAMRIS synovitis score 
by MRI imaging
To explore the durability of effect of 
LY3462817

Proportion of participants achieving LDA (with the 
following measures: DAS28-CRP, DAS28-ESR, 
SDAI, and CDAI) at Week 12 and maintaining LDA 
through Week 24

Proportion of participants that achieve remission (with 
the following measures: DAS28-CRP, DAS28-ESR, 
SDAI, and CDAI) at Week 12 and maintaining 
remission through Week 24
Abbreviations: ACR = American College of Rheumatology; ACR20 = 20% improvement in American College of 
Rheumatology criteria; ACR50 = 50% improvement in American College of Rheumatology criteria; 
ACR70 = 70% improvement in American College of Rheumatology criteria; AE = adverse event; 
CDAI = Clinical Disease Activity Index; CRP = C-reactive protein; DAS28 = Disease Activity Score modified to 
include the 28 diarthrodial joint count; ESR = erythrocyte sedimentation rate; HAQ-DI = Health Assessment 
Questionnaire-Disability Index; LDA = low disease activity; MRI = magnetic resonance imaging; 
PRO = patient-reported outcome; RA = rheumatoid arthritis; RAMRIS = Rheumatoid Arthritis Magnetic 
Resonance Imaging Scoring system; SAE = serious adverse event; SDAI = Simplified Disease Activity Index; 
SF-36 = Study 36-Item Short Form Health Survey; VAS = visual analog scale.

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
23
4.
Study Design
4.1.
Overall Design
This is a Phase 2, proof-of-concept, placebo-controlled, double-blind, randomized study in adult 
participants with moderately to severely active RA who have had an inadequate response to 
csDMARDs, or to bDMARDs/tsDMARDs. Participants will be administered LY3462817 or 
placebo IV Q4W.
Screening Period (Visit 1, Days -42 to -1)
Participants will sign the informed consent document(s) at Visit 1, prior to completion of any 
procedures. Participants will be evaluated for study eligibility ≤42 days prior to the baseline visit 
(Visit 2).  
Period 1: Double-blind Treatment (Visits 2 to 6; 12 weeks)
At the baseline visit (Visit 2), participants who fulfill the eligibility criteria will be randomized to 
receive LY3462817 700 mg, LY3462817 300 mg, or placebo in an allocation ratio of 2:1:1.
The double-blind treatment period will establish the clinical efficacy and safety of LY3462817.
The study will be evaluated for the primary objective at the end of the double-blind treatment 
period.
Period 2 (Visits 6 to 10; 12 weeks)
Data from a Study KDAC interim analysis that includes Week 12 data from participants in the
KDAC 700-mg cohort, must be reviewed prior to a participant proceeding to Period 2 in Study 
KDAD.
At Week 14, participants will be evaluated for clinical benefit. 
Participants assigned to LY3462817 at baseline, and achieving low disease activity (CDAI ≤10) 
at Week 14 will continue to receive LY3462817 at the randomized dose through Week 24 to 
assess safety and tolerability and evaluate efficacy.  
All other participants at Week 14, regardless of baseline treatment assignment, will stop study 
drug infusions and should receive standard of care treatment at the investigator’s discretion.
Posttreatment Safety Follow-up Period (Visits V801 and 802; 12 weeks)
Following Period 2, participants will be followed posttreatment for 12 weeks to assess safety, 
study drug exposure, and clinical disease activity measures. Participants who discontinue the 
study intervention per Section 7 will have their last visit at 12 weeks from the last administration 
of the study intervention.
4.2.
Scientific Rationale for Study Design
Appropriateness of study population
Patients with RA are treated with the oral csDMARD methotrexate (MTX) as the first-line 
therapy either by itself or in combination with other therapies (Smolen et al. 2020). If the 
treatment target is not achieved with the initial csDMARD strategy, treatment modification often 

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
24
involves use of bDMARDs, including tumor necrosis factor-α (TNF-α) inhibitors, or targeted 
synthetic tsDMARDs, in combination with csDMARDs (Smolen et al. 2020).
LY3462817 is being investigated to modulate the underlying immune dysregulation in the PD-1 
pathway for the treatment of RA. Enrolling a mixed RA population who have had an inadequate 
response to csDMARDs, or to bDMARDs/tsDMARDs would allow patients with inadequate 
response to the current standard of care for RA across the disease spectrum to be included in the 
study.
Duration of treatment period and post-treatment follow-up
The placebo-controlled treatment period (Period 1) lasts 12 weeks. Participants randomized to 
LY3462817 at baseline can continue to receive treatment though Week 24 if achieving low 
disease activity by Week 14. Per current RA treatment guidelines (Smolen et al. 2020), therapy 
should be adjusted if no improvement is achieved by approximately ≤3 months within initiation, 
or if the target has not been reached by 6 months (Smolen et al. 2020). All participants
randomized to placebo, and participants randomized to LY3462817 not achieving low disease 
activity by Week 14 should be switch to SOC RA therapy at the investigator’s discretion. The 
length of the study placebo-controlled period falls within those guidelines.
The 12-week follow-up duration after 24 weeks of treatment is considered to be sufficient to 
evaluate safety and to explore the durability of biomarker and clinical disease activity changes 
achieved during the 24-week treatment period. Participants with disease activity that require any 
other treatment may discontinue the study at any time (Section 7.2).
Change from baseline in DAS28-CRP as the primary endpoint
The primary endpoint of this study is the change from baseline at Week 12 in the Disease 
Activity Score - C-reactive protein (DAS28-CRP) (Sections 3 and 8.1.1) and is a continuous 
measure that enables evaluation across multiple time points.
MRI
Magnetic resonance imaging (MRI) allows detailed assessment of the synovial joint. Magnetic 
resonance imaging features are frequently used as outcome measures in RA clinical trials. The 
Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) RA MRI Scoring 
system (RAMRIS) outlines semiquantitative scoring of 5 RA pathologies: bone erosions, joint 
space narrowing, synovitis, tenosynovitis, and bone marrow edema in the wrist and 
metacarpophalangeal joints.
The primary interest in this study is to evaluate the effectiveness of LY3462817 in reducing 
inflammation in the joints. Enrolling study participants with active synovitis as determined by 
MRI will support overall evaluation of LY3462817 in reducing inflammation. Exploratory 
evaluation of a change in RAMRIS synovitis score at Week 12 will provide an objective measure 
of reduction in inflammation.
4.3.
Justification for Dose
In this study, 2 dose levels of LY3462817 will be evaluated: 300 mg and 700 mg. These dose 
levels were selected based on preclinical pharmacology and toxicology data, and available 
clinical PK, target engagement, and safety data.

CONFIDENTIAL
Protocol number J1A-MC-KDAD(b)
25
In Study KDAB, single LY3462817 IV doses of 350 and 700 mg have been evaluated in healthy 
subjects with no clinical significant safety concerns. The ongoing Study KDAC, is designed to 
evaluate multiple doses (4 total doses) of 75 mg, 300 mg, and 700 mg of LY3462817 IV Q4W in 
participants with psoriasis. The data from these studies and the plan to initiate KDAD is 
discussed in Section 2.2.
From available human PK and preclinical monkey toxicology data, the estimated margins of 
safety for 300 mg and 700 mg LY3462817 IV Q4W are ≥24 and >10-fold, respectively, based on 
both dose and steady-state exposure multiples. 
The planned dose levels were also selected to evaluate an exposure range that is anticipated to be 
pharmacologically active. Receptor occupancy was used as a surrogate for pharmacological 
activity to help assess dose levels that saturate the target over the planned dosing interval. Doses 
of 350 mg and 700 mg have both been shown to saturate the receptor in plasma over 4 weeks and 
longer. However, significant uncertainties exist in translating RO profile in plasma to tissue with 
respect to drug concentration and receptor density (Chen et al. 2015; Rao et al. 2017). The 2 dose 
levels help account for these uncertainties, both of which directionally point to a decrease in 
extent and duration in tissue RO relative to plasma. Additionally, inclusion of 2 dose levels in 
KDAD will allow for a direct comparison with the corresponding dose levels in KDAC for 
assessing the impact, if any, of disease state on PK, RO, and sPD-1. If there is impact, having an 
additional dose level in KDAD will provide more data and confidence when projecting forward 
to a dose level or regimen ranging study.
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all required 
phases of the study including the last scheduled procedure shown in the SoA (Section 1.3).
The end of the study is defined as the date of last scheduled procedure shown in the SoA for the 
last participant in the trial globally.

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Protocol number J1A-MC-KDAD(b)
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5.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Are ≥18 years of age, at the time of signing the informed consent
Type of Participant and Disease Characteristics
2. Have a diagnosis of adult onset RA as defined by the 2010 American College of 
Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification 
criteria (Aletaha et al. 2010) for at least 3 months prior to screening
3. Have moderately to severely active RA defined by the presence of ≥6 swollen joints 
(based on 66 joint count) and ≥6 tender joints (based on 68 joint count) at screening and 
baseline. The distal interphalangeal joint should be evaluated but not included in the total 
count to determine eligibility
4. Have at least 1 of the following: 

positive test results for rheumatoid factor or anti-citrullinated peptide antibodies at 
screening, 
OR 

previous radiographs documenting bony erosions in hands or feet consistent with RA
5. Have C-reactive protein (CRP) >1.2 times upper limit of normal (ULN) per the central
laboratory at screening
6. Have active synovitis in ≥1 joint in hands or wrists at screening as demonstrated by a 
MRI synovitis RAMRIS score (Østergaard et al. 2017) of ≥1 determined from central 
reading of images
7. Vaccinations of study subjects should be up to date per regional and national guidelines, 
specifically influenza, pneumonia, and zoster. All should be administered ≥30 days 
before randomization and no live vaccines should be used within 3 months of 
randomization  
8. Have clinically acceptable central laboratory test results at screening (retesting is allowed 
for hematology and chemistry), as assessed by the investigator, including:
Hematology

absolute neutrophil count ≥1.5 × 109/L (≥1.5 × 103/µL or ≥1.5 GI/L)

platelet count ≥100 × 109/L (≥100 × 103/µL or ≥100 GI/L)

hemoglobin level ≥10.0 g/dL

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Protocol number J1A-MC-KDAD(b)
27

lymphocyte count >500 cells/µL (>0.50 × 103/µL or >0.50 GI/L)

total leukocyte count ≥3.0 × 109/L (≥3.0 × 103/µL or ≥3.0 GI/L)
Clinical chemistry test results

serum creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase 
(AST) levels ≤2 × ULN

total bilirubin level (TBL) and alkaline phosphatase (ALP) <1.5 × ULN (patients 
with Gilbert’s syndrome must have serum direct bilirubin <1.5 mg/dL)
Concomitant Therapy
9. Demonstrated an inadequate response to, or loss of response or intolerance to:

at least 1 csDMARD treatment
OR

at least 1 bDMARD/tsDMARD treatment 
This is defined as signs and symptoms of persistently active disease despite a history of
treatment with at least 1 of the following: azathioprine, MTX, hydroxychloroquine, 
leflunomide, sulfasalazine, bDMARDs, or tsDMARDs
10. The following therapies are permitted during the study, if the dose is stable for ≥4 weeks 
prior to the screening MRI:

parenteral MTX up to 20 mg/week OR oral MTX up to 25 mg/week. Subjects on 
MTX should receive supplementation with folic acid according to local standard of 
care

hydroxychloroquine up to 400 mg/day

leflunomide up to 20 mg/day

oral sulfasalazine up to 3000 mg/day 

oral prednisone ≤10 mg daily or other equivalent corticosteroid dose
Contraception
11. To participate in the study, participants must agree to the reproductive and contraceptive 
agreements and guidance provided in Section 10.4, Appendix 4.  
Contraceptive use by men or women should be consistent with local regulations for those 
participating in clinical studies.
Informed Consent
12. Capable of giving signed informed consent as described in Appendix 1 which includes 
compliance with the requirements and restrictions listed in the informed consent form 
(ICF) and in this protocol

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Protocol number J1A-MC-KDAD(b)
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5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
13. Class IV RA according to ACR revised response criteria
14. Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the 
investigator, increases the risks associated with participating in the study
15. Have presence of 1 or more significant concurrent medical conditions per investigator 
judgment, including but not limited to the following: poorly controlled diabetes or 
hypertension; chronic kidney disease stage IIIb, IV, or V; symptomatic heart failure (New 
York Heart Association class II, III, or IV); myocardial infarction or unstable angina 
pectoris within the past 12 months prior to randomization; severe chronic pulmonary 
disease (e.g., requiring oxygen therapy); and major chronic inflammatory disease or 
connective tissue disease other than RA
16. Have a history of chronic alcohol abuse, IV drug abuse or illicit drug abuse within 1 year 
before screening.
Note: Marijuana use is prohibited during participation in this study, regardless of local 
laws or if used for medical purposes. Cannabidiol (CBD) products may be used during 
the study if they are derived exclusively from hemp. Participants who use hemp-based 
CBD products must be on a stable dose for at least 10 days prior to randomization, and 
participants must remain on that stable dose during the study.
17. Have a Columbia-Suicide Severity Rating Scale (C-SSRS) ideation within 1 month prior 
to screening or any suicidal behavior within 3 months prior to screening and either 
ideation or suicidal behavior during screening prior to Visit 2
18. Have donated blood of more than a single unit of blood within 4 weeks before 
randomization (Visit 2) or intent to donate blood during the course of the study
19. Have a diagnosis or history of malignant disease within 5 years prior to baseline, with the 
exceptions of:

basal cell or squamous epithelial carcinomas of the skin that have been 
resected with no evidence of metastatic disease for 3 years, or 

cervical carcinoma in situ, with no evidence of recurrence within the 5 years 
prior to baseline
20. Have presence of confirmed cervical dysplasia
21. Have had any surgical procedure (except for minor surgery requiring local or no 
anesthesia and without any complications or sequelae) within 12 weeks prior to 
screening, or any planned surgical procedure scheduled to occur during the study

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Protocol number J1A-MC-KDAD(b)
29
22. Have received a Bacillus Calmette-Guerin (BCG) vaccination or BCG treatment within 
12 months of screening; or received any other live vaccine(s) (i.e., live attenuated) within 
3 months of screening, or intend to receive a live vaccine during the study
23. Have had any of the following types of infection within 3 months of screening or 
develops any of these infections before the randomization visit:
o
Serious (requiring hospitalization, and/or IV or equivalent oral antibiotic treatment) 
o
Opportunistic (as defined in Winthrop et al. 2015) 
o
Herpes zoster is considered active and ongoing until all vesicles are dry and 
crusted over
o
Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer) 
o
Recurring (including, but not limited to herpes simplex, herpes zoster, recurring 
cellulitis, chronic osteomyelitis) 

Subjects with recurrent nonserious infections such as cellulitis and 
uncomplicated orolabial and/or genital herpes may be enrolled at the discretion 
of the investigator when deemed not to place subjects at an increased risk of 
complications
24. Have any of the following:

Human immunodeficiency virus (HIV) infection

Current infection with hepatitis B virus (HBV) (i.e., positive for hepatitis B surface 
antigen and/or polymerase chain reaction [PCR] positive for HBV DNA)

Current infection with hepatitis C virus (HCV) (i.e., positive for HCV RNA) 

Active tuberculosis (TB)
25. Have or have had latent TB infection (LTBI) that has not been treated with a complete 
course of appropriate therapy as defined by the World Health Organization (WHO) 
and/or the United States Centers for Disease Control and Prevention (CDC), unless such 
treatment is underway, as per Section 8.2.6.
26. Current or recent acute active infection, or fever of 100.5°F (38°C) or above, at screening 
or baseline. For at least 30 days prior to screening, participants must have no symptoms 
and/or signs of confirmed or suspected infection, and must have completed any 
appropriate anti-infective treatment
27. Have estimated glomerular filtration rate from serum creatinine using the Modification of 
Diet in Renal Disease method of <60 mL/minute  
28. Participants having contraindications to MRI (for example, claustrophobia, pacemakers, 
aneurysm clips, intraocular metallic fragments) or IV gadolinium diethylenetriamine 
penta-acetic acid ([Gd-DTPA]; moderate or severe renal insufficiency, prior allergic 
reaction to gadolinium-containing contrast media)
29. Are women who are currently pregnant or breastfeeding, or who intend to become 
pregnant or to breastfeed at any time during the study or within 20 weeks after receiving 
the last dose of study drug.

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Protocol number J1A-MC-KDAD(b)
30
Prior/Concomitant Therapy
30. Currently receiving or have received any of the following therapies within 28 days prior 
to the screening MRI:

MTX, hydroxychloroquine, sulfasalazine, or leflunomide at an unstable dose
(defined as a change in prescription).
This also includes a planned dose change during the study (including initiation or 
discontinuation)

Cyclophosphamide, azathioprine, cyclosporine, gold, mycophenolate mofetil, 
Prosorba column, or Tacrolimus

Oral Janus kinase inhibitor (e.g., tofacitinib, baricitinib)

Parenteral corticosteroids, including initiation of planned treatment during the study
Note: A single intra-articular corticosteroid injection is permitted within 28 days 
prior to the screening MRI if no more than 40 mg triamcinolone (or equivalent) is 
administered and no further injections are planned during the study. The treated joint 
should be excluded from any joint-specific evaluations during the study.

A chronic narcotic drug at an unstable dose. This also includes planned increase/new 
prescription during the study
31. Have received any of the following biologic immunosuppressive therapies under the 
defined conditions or plan any such treatments during the study (other biologic agents 
may be allowed after discussion with the sponsor and upon agreement in writing):

Etanercept, adalimumab, anakinra, infliximab, certolizumab pegol, golimumab, 
abatacept, or tocilizumab within 8 weeks prior to screening MRI

B-cell–depleting agents (such as rituximab) or other cell-depleting biologics (e.g., 
anti-CD3 antibody) within 12 months prior to screening MRI
32. Have failed more than 2 bDMARDs or tsDMARDs (e.g. excluded if have failed 
2 bDMARDs and 1 tsDMARD)
33. Have previously completed a clinical trial investigating any other molecule targeting 
PD-1 or have previously discontinued from this study after receiving LY3462817
Prior/Concurrent Clinical Study Experience
34. Are currently enrolled in any other clinical trial involving a study intervention 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 trial involving study intervention.
If the previous study intervention has a long half-life, 3 months or 5 half-lives (whichever 
is longer) should have passed prior to screening
36. Have previously completed or withdrawn from this study

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Protocol number J1A-MC-KDAD(b)
31
Other Exclusions
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 employees or employees of third-party organizations involved with the study 
that require exclusion of their employees
39. Are not willing to receive IV injections
40. Are unsuitable for inclusion in the study, in the opinion of the investigator or sponsor, for 
any reason that may compromise the participant’s safety or confound data interpretation
5.3.
Lifestyle Considerations
All study participants should be instructed not to donate blood or blood products during the study 
or for 6 months after the last dose of the study intervention.
Reproductive and Contraceptive guidance is provided in Section 10.4, Appendix 4.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened only once for failure due to any of the following criteria: 2, 8, 21, 22, 23, 26, 34, or 
35. Individuals who failed criterion 25 can be rescreened once if appropriate treatment for LTBI 
is underway. Rescreened participants should be assigned a new participant number. Each time 
rescreening is performed, the individual must sign a new ICF.

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Protocol number J1A-MC-KDAD(b)
32
6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
6.1.
Study Intervention(s) Administered
Study interventions
Each participant will receive multiple IV infusions of placebo, LY3462817 300 mg, or 
LY3462817 700 mg.
Intervention Name
Placebo
LY3462817
LY3462817
Dose Formulation
0.9% sodium chloride 
solution
Solution
Solution
Unit Dose Strengths
-
50 mg/mL in a 3-mL vial
Dosage Level(s)
(mg)
Not applicable
300
700
Use
Placebo
Experimental
IMP and NIMP
IMP
IMP
Sourcing
Commercially available 
0.9% sodium chloride 
solution sourced centrally by 
Lilly
From Lilly
Packaging and 
Labeling
Commercially available 
0.9% sodium chloride 
solution
Study intervention will be provided in glass vials and will 
be labeled as required per country requirement
Abbreviations: IMP = Investigational Medicinal Product; NIMP = Noninvestigational Medicinal Product.
Study intervention will be prepared by an unblinded pharmacy staff or pharmacist who is not 
involved in any other study-related procedures.
The study intervention is planned to be administered as an IV infusion. 
The infusion rate may be reduced as deemed necessary if an infusion reaction is observed 
(Section 8.3.6). Participants will be monitored for signs and symptoms of infusion reaction:

during the infusion, and 

for at least 1 hour after completion of the infusion. 
Infusion information may be found in the pharmacy binder.
Resuscitation equipment, emergency drugs, and appropriately trained medical staff must be 
available during the infusion and for at least 1 hour after the completion of the infusion.

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Protocol number J1A-MC-KDAD(b)
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6.2.
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate storage conditions have been maintained 
during transit for all study intervention received and any discrepancies are reported and resolved 
before use of the study intervention.
Only participants enrolled in the study may receive study intervention and only authorized study 
staff or designee may supply or administer study intervention. All study intervention must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized study staff or designee.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records).
Further guidance and information for the final disposition of unused study interventions are 
provided in the pharmacy manual.
6.3.
Measures to Minimize Bias: Randomization and Blinding
To preserve the blinding of the study, a minimum number of Lilly personnel who are not directly 
involved with investigational sites will see the randomization table and treatment assignments 
before the study is complete.
Joint, disease activity, and safety assessments 
Joint Assessor
To prevent potential bias due to observed efficacy or laboratory changes, a “dual assessor” 
approach will be used to evaluate efficacy and safety. The Joint Assessor (or designee) should be 
a rheumatologist or skilled arthritis assessor. The Joint Assessor will be responsible for 
completing the joint counts. To ensure consistent joint evaluation throughout the trial, individual 
participants should be evaluated by the same Joint Assessor for all study visits. The Joint 
Assessor must not access or discuss with the participant the patient-reported assessments, 
Physician’s Global Assessment of Disease Activity (PhGADA_VAS), and safety assessments.
Safety Assessor
The Safety Assessor (or designee) should be a rheumatologist (or medically qualified physician) 
and will have access to both safety and efficacy data. The Safety Assessor may be the principal 
investigator. The Safety Assessor will be responsible for completing the PhGADA_VAS. To 
ensure consistent PhGADA_VAS throughout the trial, the instrument should be evaluated by the 
same physician at all study visits. The Safety Assessor will have access to source documents, 
laboratory results, and electronic case report forms (eCRFs) and will be responsible for making 
treatment decisions based on a participant’s clinical response and laboratory parameters.
Method of treatment assignment
Assignment to treatment groups will be determined by a computer-generated random sequence 
using an interactive web-response system (IWRS).

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Protocol number J1A-MC-KDAD(b)
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Participants will be stratified by prior use of csDMARD only or by tsDMARD/bDMARDs use 
(yes versus no).
Emergency unblinding
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a participant’s treatment assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If a participant’s treatment assignment is 
unblinded, the sponsor must be notified immediately.
Emergency unblinding for AEs may be performed through the IWRS. This option may be used 
ONLY if the participant’s well-being requires knowledge of the participant’s treatment 
assignment. All calls resulting in an unblinding event are recorded and reported by the IWRS.
6.4.
Study Intervention Compliance
Study intervention will be administered under medical supervision by the investigator or 
designee. The date and time of each dose administered will be recorded in the source documents 
and in the case report form (CRF). The dose of study intervention and study participant 
identification will be confirmed prior to the time of dosing.
6.5.
Concomitant Therapy
Participants 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.
Additional drugs are to be avoided during the study unless required to treat an AE or for the 
treatment of an ongoing medical condition. Investigators should follow local guidelines for the 
management of lipid disorders. If the need for other concomitant medications arises, 
discontinuation of the participant from study intervention or the study will be at the discretion of 
the investigator in consultation with sponsor (or designee).
All medications, whether prescription or over-the-counter, used at screening and/or during the 
study must be documented in the eCRF with start and stop dates.
6.5.1.
Permitted Rheumatoid Arthritis Concomitant Therapy
Treatment with the following concomitant medications for RA during the study are permitted as 
outlined below and in the inclusion/exclusion criteria. This applies to all participants during 
Period 1 and any participant that remains on LY3462817 during Period 2.
Concomitant therapy
Permitted
Not permitted
Methotrexate (MTX)
If parenteral, up to 20 mg/week
If oral, up to 25 mg/week
Subjects on MTX should receive supplementation 
with folic acid according to local standard of care
Hydroxychloroquine
up to 400 mg/day
Oral sulfasalazine
up to 3000 mg/day

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Protocol number J1A-MC-KDAD(b)
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Concomitant therapy
Permitted
Not permitted
Leflunomide
up to 20 mg/day
Nonsteroidal anti-
inflammatory drugs 
(NSAIDs)
Permitted during the Period 1 only if the participant 
was on a stable dose for at least 7 days before 
planned randomization. 
Increase of NSAID dose and/or 
introduction of new NSAIDs are 
not permitted during the Period 1 
or in participants receiving
LY3462817 in Period 2
Analgesics
Dose reductions and/or termination of analgesics 
are permitted at any time.
Corticosteroids
Prednisone (or equivalent) at doses up to 10 mg per 
day is allowed during this study but must be 
maintained at stable levels from ≥4 weeks prior to 
the screening magnetic resonance imaging (MRI)
through Period 1 or in participants receiving 
LY3462817 in Period 2.
Topical, intranasal, intraocular, and inhaled 
corticosteroids are permitted.
Directions for use of intra-articular 
glucocorticoids:
If an unforeseen intra-articular glucocorticoid 
injection is required during the study, it will be 
noted as a protocol deviation.
Any joints that had been injected with intra-articular 
corticosteroids within 42 days prior to the screening 
MRI will be censored from the clinician-
administered Tender Joint Counts (TJCs) and 
Swollen Joint Counts (SJCs) (68/66) for the 
duration of the study.
Participants who were not 
previously on prednisone (or 
equivalent) prior to 
randomization should not initiate 
corticosteroid therapy during the 
study during Period 1 or in 
participants receiving 
LY3462817 in Period 2, 
Participants should not receive 
other systemic corticosteroids 
during the study including 
intra-muscular or intra-articular 
corticosteroids during Period 1 or 
in participants receiving
LY3462817 in Period 2. 
Folic acid
Local standard of care should be followed for 
concomitant administration of folic acid.
6.5.2.
Prohibited Concomitant Therapy
Live vaccinations are not allowed up to 3 months prior to screening or at any time during the 
study. Live herpes zoster vaccination is not permitted within 30 days of planned randomization 
or at any time during the study.
Nonlive seasonal vaccinations and/or emergency vaccination, such as rabies or tetanus 
vaccinations, are allowed.
6.5.3.
Standard of Care Therapy after Week 14 
All placebo patients should begin SOC therapy at Week 14 at the investigator’s discretion. 
Participants randomized to LY3462817 at baseline and not achieving low disease activity 
(CDAI ≤10) at Week 14 will no longer receive study drug infusions and should receive SOC 
therapy at the investigator’s discretion.   

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Protocol number J1A-MC-KDAD(b)
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Participants who achieve low disease activity at Week 14, and maintain treatment with 
LY3462817 during Period 2, can be switched to SOC prior to Week 24 if the participant stops 
receiving clinical benefit. Name(s) and dosage regimen(s) must be recorded for the SOC therapy.
Standard of care medications will not be supplied by the sponsor.
6.6.
Dose Modification
Dose modifications during the treatment period will not be allowed.
6.7.
Intervention after the End of the Study
No continued access is planned after completion of this study, as additional efficacy would be 
needed to demonstrate continued access criteria.

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Protocol number J1A-MC-KDAD(b)
37
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
The sections below describe reasons for a participant’s

temporary or permanent discontinuation of study intervention (Section 7.1), or

discontinuation (withdrawal) from the study (Section 7.2).
Discontinuation of specific sites or of the trial as a whole are handled as part of regulatory, 
ethical, and trial oversight considerations in Section 10.1, Appendix 1.
7.1.
Discontinuation of Study Intervention
Study intervention may be temporarily withheld or permanently discontinued during the study.
Participants who permanently discontinue study intervention early will undergo early termination 
procedures, which include an early termination visit and a posttreatment follow-up visit (V801)
as described in the SoA (Section 1.3).
The investigator will complete any AE reporting and follow-up (Section 8.3).
7.1.1.
Criteria for Temporary Interruption (Withholding) of Study Intervention
Study treatment may be temporarily discontinued if the participant requires surgery. 
Administration of the study intervention may be restarted only after adequate wound healing.  
This and other situations that may merit temporary discontinuation of the study intervention 
should be discussed with the sponsor. The investigator should consult with the Medical Monitor  
and then determine when it is appropriate to recommence study treatment.  
7.1.1.1.
Infection-related Criteria for Temporary Withholding of Study Intervention
Study intervention will be temporarily withheld if any of the following infection-related criteria 
occur during the study:
1. Serious or opportunistic infections, as defined in Exclusion Criteria (Section 5.2). Study 
intervention can be withheld until resolution of all acute clinical signs and symptoms, and 
completion of all appropriate anti-infective treatment (exception for LTBI, noted below). The 
investigator should consult with the Medical Monitor and then determine when it is 
appropriate to recommence study treatment. 
2. If a participant is diagnosed with LTBI during the study and is treated for LTBI as follows: 
a) Study intervention is temporarily held for at least the first 4 weeks of LTBI treatment.
b) If there is no evidence of hepatotoxicity (ALT/AST must remain ≤2 times ULN) or other 
treatment intolerance after receiving at least 4 weeks of appropriate LTBI therapy (as per 
WHO and/or CDC guidelines), then study intervention may be resumed. 
c) The participant must complete appropriate LTBI therapy during the course of the study to 
remain eligible to continue to receive study intervention.
3. HBV DNA results reported as positive, or as detecting HBV DNA, but HBV DNA is below 
the level of quantification. The Medical Monitor should be contacted regarding study status 

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Protocol number J1A-MC-KDAD(b)
38
of the participant. Hepatitis B virus DNA testing should be repeated as soon as possible. If 
HBV DNA is confirmed positive, then study intervention should be discontinued.
7.1.2.
Criteria for Permanent Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If study intervention is definitively discontinued, the 
participant will be encouraged to remain in the study. See the SoA for data to be collected at the 
time of discontinuation of study intervention and follow-up and for any further evaluations that 
need to be completed.
Permanent discontinuation of study intervention should occur if the scenarios described occur 
during the study.
Participant decision

The participant requests to discontinue the study intervention.
Investigator decision

The investigator decides that the participant should be discontinued from the 
study intervention.
Pregnancy

The participant becomes pregnant during the study (see Section 8.3.5 and 
Section 10.4, Appendix 4).
Safety considerations
The participant:

Has a malignancy (except for successfully treated basal or squamous cell skin carcinoma)

Answered "yes" to Question 4 or Question 5 on the "Suicidal Ideation" portion of the 
C-SSRS

Answered "yes" to any of the suicide-related behaviors on the Suicidal Behavior portion
of the C-SSRS
A psychiatrist or appropriately trained professional may assist in the decision to 
discontinue the participant.

Is diagnosed with LTBI during the study and are not a candidate for treatment as 
described in Section 7.1.1.1, or

Has a serious or opportunistic infection that in the opinion of the investigator merits the 
study intervention being discontinued. Such infections may include, but are not limited 
to:
o
HIV/acquired immune deficiency syndrome (AIDS) infection
o
active TB infection or untreated LTBI (see Sections 7.1.1 and 8.2.6)
o
HCV RNA positive (Section 8.2.8)
o
HBV DNA positive (Section 8.2.7).
The participant should be referred to, evaluated and managed by a specialist physician with 
expertise in evaluation and management of viral hepatitis prior to discontinuation of any 

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Protocol number J1A-MC-KDAD(b)
39
immunomodulatory and/or immunosuppressive therapy, including study intervention. Timing of 
discontinuation from study intervention relative to the initiation of any antiviral treatment for 
hepatitis is to be based on the recommendation of the consulting specialist physician, in 
conjunction with the investigator, and aligned with medical guidelines and standard of care.
Hepatic event or liver test abnormality
Participants who are discontinued from intervention due to a hepatic event or liver test 
abnormality should have additional hepatic safety data collected via eCRF. The investigator 
should consult with the medical monitor to determine if discontinuation of the intervention for 
abnormal liver tests should be considered if a participant meets one of these conditions (see 
Section 10.7, Appendix 8):

ALT or AST >8 times ULN

ALT or AST >5 times ULN for more than 2 weeks

ALT or AST >3 times ULN and TBL >2 times ULN or international normalized 
ratio (INR) >1.5 

ALT or AST >3 times ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

ALP >3 times ULN

ALP >2.5 times ULN and TBL >2 times ULN, or 

ALP >2.5 times ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
See the SoA for data to be collected at the time of intervention discontinuation and follow-up and 
for any further evaluations that need to be completed.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study:
●
at any time at his/her own request 
●
at the request of his/her designee (for example, legal guardian)
●
at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons
●
if the participant becomes pregnant during the study
●
if enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study
●
if the participant, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the new agent
Discontinuation is expected to be uncommon.

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At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA. See SoA (Section 1.3) for data to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be completed.
The participant will be permanently discontinued from the study intervention.
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant
withdraws from the study, he/she may request destruction of any samples taken and not tested,
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued from study treatment unless 
there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment. Additional country-specific requirements for discontinuation of 
inadvertently enrolled participants is provided in Section 10.10, Appendix 10.
The investigator should consult with the Medical Monitor, then determine if it is medically 
appropriate to continue. The investigator must obtain documented approval from the Medical 
Monitor to allow the inadvertently enrolled participant to continue in the study with or without 
treatment with investigational product.
Safety follow up is as outlined in:

Section 1.3 (SoA)

Section 8.2 (Safety Assessments), and

Section 8.3 (Adverse Events and Serious Adverse Events).
7.3.
Lost to Follow up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including those 
who did not get study intervention. Public sources may be searched for vital status information.
If vital status is determined to be deceased, this will be documented and the participant will not 
be considered lost to follow-up. Sponsor personnel will not be involved in any attempts to collect 
vital status information.
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1, 
Appendix 1.

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8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA. Protocol waivers or exemptions 
are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential participants
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable.
Monitoring of blinded safety data will continue throughout the study and will be conducted by 
blinded study team members. Details of the blinded safety reviews, including the frequency and 
approximate timing, are specified in the trial level safety review plan.
8.1.
Efficacy Assessments
All patient-reported and clinician-reported efficacy assessments will be captured on an electronic 
tablet collected at site visits.
8.1.1.
Disease Activity Score–High-Sensitivity C-Reactive Protein (DAS28-hsCRP)
The DAS28-hsCRP measures disease activity in 28 joints using a composite numeric score of the 
following variables (Vander Cruyssen et al. 2005): 

TJC (see Section 8.1.4)

SJC (see Section 8.1.4)

high sensitivity C-reactive protein (hsCRP), and

Patient’s Global Assessment of Disease Activity (PaGADA_VAS; see Section 8.1.7).
The 28 joints examined and assessed as tender or not tender for TJC and as swollen or not 
swollen for SJC include 14 joints on each side of the participant’s body (Smolen et al. 1995): 

the 2 shoulders

the 2 elbows

the 2 wrists

the 10 metacarpophalangeal joints

the 2 interphalangeal joints of the thumb

the 8 proximal interphalangeal joints, and

the 2 knees.
8.1.2.
Disease Activity Score–Erythrocyte Sedimentation Rate (DAS28-ESR)
The DAS28-ESR measures disease activity in 28 joints using a composite numeric score of the 
following variables (Vander Cruyssen et al. 2005): 

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
TJC (Section 8.1.4)

SJC (Section 8.1.4)

Erythrocyte sedimentation rate (ESR), and

PaGADA_VAS (Section 8.1.7).
For description of the 28 joints to be examined, see Section 8.1.1.
The DAS28-ESR remission is defined as DAS28-ESR <2.6, and DAS28-ESR LDA is defined as 
DAS28-ESR ≤3.2.
8.1.3.
American College of Rheumatology Criteria (ACR20, ACR50, and ACR70)
The ACR20 is defined as at least 20% improvement in the ACR core set values. Similarly, 
ACR50 and ACR70 are defined as at least 50% and 70% improvement in the ACR core set 
values.
This is defined as:

an improvement of at least 20%, 50%, or 70% in the TJC and SJC (68/66; Section 8.1.4)
AND

an improvement of at least 20%, 50%, or 70% in at least 3 of the following 
5 assessments:
1. Patient’s Global Assessment of Arthritis Pain (visual analog scale [VAS]; 
Section 8.1.6)
2. PaGADA_VAS (Section 8.1.7)
3. PhGADA_VAS (Section 8.1.5)
4. Patient’s Assessment of Physical Function as measured by the Health Assessment 
Questionnaire-Disability Index (HAQ-DI; Section 8.1.8)
5. Acute phase reactant as measured by hsCRP
8.1.4.
Tender Joint Count and Swollen Joint Count
The joint exam will be performed by the Joint Assessor and reviewed by the Safety Assessor 
(Section 6.3).
8.1.5.
Physician’s Global Assessment of Disease Activity (PhGADA_VAS)
The PhGADA_VAS is used as a component of ACR (Section 8.1.3) as well as a separate 
efficacy assessment.
The PhGADA_VAS is a single item that asks the physician to assess the patient’s current disease 
activity on a 0- to 100-mm VAS, with anchors of 0 = “no disease activity” and 100 = “extremely 
active disease.”
8.1.6.
Patient’s Global Assessment of Arthritis Pain (Visual Analog Scale)
The Patient’s Global Assessment of Arthritis Pain (VAS) is used as a component of ACR 
(Section 8.1.3) as well as a separate efficacy assessment.

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The Patient’s Global Assessment of Arthritis Pain (VAS) is a single item that asks the patient to 
rate the current severity of their pain in relation to their RA on a 0- to 100-mm VAS, with 
anchors of “no pain” and “worst possible pain.”
8.1.7.
Patient’s Global Assessment of Disease Activity (PaGADA_VAS)
The PaGADA_VAS is used as a component of ACR (Section 8.1.3) as well as a separate 
efficacy assessment.
The PaGADA_VAS is a single item that asks the patients to indicate how they feel their RA is 
today on a 0- to 100-mm VAS, with anchors of 0 = “very well” and 100 = “very poor.”
8.1.8.
Health Assessment Questionnaire - Disability Index (HAQ-DI)
The HAQ-DI is used as a component of ACR (Section 8.1.3) as well as a separate efficacy 
assessment.
The HAQ-DI is a patient-reported questionnaire that is commonly used in RA to measure 
disease-associated disability (assessment of physical function). It consists of 24 questions 
referring to 8 domains (Fries et al. 1980, 1982; Ramey et al. 1996): 
1. dressing/grooming
2. arising
3. eating
4. walking
5. hygiene
6. reach
7. grip, and
8. activities. 
Participants use a scale from 0 to 3 to score difficulty when performing these and other daily 
activities over the past week (0 = without any difficulty, 1 = with some difficulty, 2 = with much 
difficulty, and 3 = unable to do). The reported use of special aids or devices and/or the need for 
assistance of another person to perform these activities is also assessed. Higher scores indicate 
more limitations in physical function. The scores for each of the functional domains will be 
averaged to calculate the functional disability index.
8.1.9.
Simplified Disease Activity Index (SDAI)
The SDAI is a tool for measurement of disease activity in RA that integrates measures of 
physical examination, acute phase response, patient self-assessment, and evaluator assessment. 
The SDAI is calculated by adding together scores from the following assessments:

number of swollen joints (0 to 28)

number of tender joints (0 to 28)

CRP in mg/dL (0.1 to 10.0)

PaGADA_VAS (0 to 100 mm), and 

PhGADA_VAS (0 to 100 mm) (Aletaha and Smolen 2005).

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Disease remission according to ACR/EULAR index-based definition of remission is defined as 
an SDAI score of ≤3.3 (Felson et al. 2011). Low disease activity is defined as an SDAI score of 
≤11.
8.1.10.
Clinical Disease Activity Index (CDAI)
The CDAI is similar to the SDAI, but it allows for immediate scoring because it does not use a 
laboratory result. The CDAI is calculated by adding together scores from the following 
assessments:

number of swollen joints (0 to 28)

number of tender joints (0 to 28)

PaGADA_VAS (0 to 100 mm), and 

PhGADA_VAS (0 to 100 mm) (Aletaha and Smolen 2005).
Remission is defined as a CDAI score of ≤2.8 (Felson et al. 2011). Low disease activity is 
defined as a CDAI score of ≤10.
8.1.11.
Medical Outcomes Study 36-Item Short Form Health Survey
The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36v2) 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 0 to 
100 scale with higher scores indicating better health status or functioning. 
In addition, 2 summary scores, the physical component score and the mental component score, 
will be evaluated based on the 8 SF-36v2 Acute domains (Brazier et al. 1992; Ware and 
Sherbourne 1992).
8.1.12.
MRI Imaging and Synovitis Score
Magnetic resonance imaging is a more sensitive, noninvasive imaging technique that can provide 
cross-sectional images in any plane allowing for simultaneous examination of all the components 
of the diarthrodial joint (including soft tissues, articular cartilage, and bone) without the need for 
ionizing radiation (McQueen and Dalbeth 2009). Specifically, both inflammatory changes (as 
represented by synovitis and osteitis) and structural changes (as represented by erosion and joint 
space narrowing) are characteristic features of RA that may be detected in patients by MRI 
imaging (Klarlund et al. 2000). 

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Magnetic resonance imaging scans will be conducted on hand/wrist determined by the 
investigator at the site, during screening and at the Week 12 visit. Screening scans will be 
evaluated to determine the presence of synovitis for study eligibility. Screening and Week 12 
scans will be read and scored in pairs for each subject by 2 assessors at a central vendor, blinded 
to each subject’s treatment and the temporal order of the scans. A detailed charter from the 
central reading laboratory will outline the MRI procedures including image acquisition, image 
analysis, and data transfer.
Synovitis, osteitis, bone erosion, and joint space narrowing scores are planned to be determined 
using the OMERACT RAMRIS system for synovitis, osteitis, and bone erosion (Østergaard et al. 
2017).
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA.
8.2.1.
Physical Examinations
A complete physical examination will be performed at the screening visit according to the SoA 
(Section 1.3). This examination excludes pelvic, rectal, and breast examinations unless clinically 
indicated.  
A symptom directed physical examination will be performed at other visits, as specified in the 
SoA and as clinically indicated. A complete physical examination may be repeated at the 
investigator’s discretion at any time a participant presents with physical complaints.
Investigators should pay special attention to clinical signs related to previous serious illnesses.
8.2.2.
Vital Signs
For each participant, vital signs measurements should be conducted according to the SoA
(Section 1.3). Vital signs include body temperature, blood pressure, and pulse rate (PR).
Participants should be seated and relaxed with both feet on the floor for at least 5 minutes before 
measurements are taken. Blood pressure and pulse should be measured using either automated or 
manual equipment. If measurements are machine averaged, the average blood pressure reading 
should be recorded on the eCRF. 
Measurements should be taken before any scheduled blood draws. 
Additional vital signs may be measured at the discretion of the investigator.
8.2.3.
Electrocardiograms
Single 12-lead ECG will be obtained as outlined in the SoA (Section 1.3) using an ECG machine 
that automatically calculates the heart rate and measures PR, and QRS and QT intervals. 
8.2.4.
Clinical Safety Laboratory Assessments
See Section 10.2, Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 

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laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those that are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within approximately 30 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified.
All protocol-required laboratory assessments, as defined in Section 10.2, Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.
If laboratory values from nonprotocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (e.g., SAE or AE or dose modification), then these 
would be reported in the AE section of the CRF.
8.2.5.
Suicidal Ideation and Behavior Risk Monitoring
Participants being treated with the study intervention should be monitored appropriately and 
observed for suicidal ideation and behavior or any other unusual changes in behavior, especially 
at the beginning and end of the course of treatment, or at the time of dose changes, either 
increases or decreases. Consideration should be given to discontinuing the study medication in 
participants who experience signs of suicidal ideation or behavior, following a risk assessment.  
Families and caregivers of participants being treated with the study intervention should be 
alerted about the need to monitor participants for the emergence of unusual changes in behavior, 
as well as the emergence of suicidal ideation and behavior and to report such symptoms 
immediately to the study investigator. 
Baseline assessment of suicidal ideation and behavior and treatment emergent suicidal ideation 
and behavior will be monitored during Study KDAD using the C-SSRS.  
C-SSRS Self-Harm Supplement and Follow-Up forms
The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicidal ideation 
and behavior during the assessment period via a questionnaire. The scale was developed by the 
National Institute of Mental Health trial group (Treatment of Adolescent Suicide Attempters 
study) for the purpose of being counterpart to the Columbia Classification Algorithm of Suicide 
Assessment (C-CASA) categorization of suicidal events.
Consistent with Food and Drug Administration (FDA) regulatory guidance (FDA 2012), any 
occurrence of suicide-related thoughts and behaviors will be assessed as indicated in the SoA 
(Section 1.3).  
The Lilly Self-Harm Supplement should be completed every time the C-SSRS is administered.
If, based on administration of the C-SSRS, it is determined that suicide-related behaviors have 

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occurred, then the Lilly Self-Harm Follow-Up form will be used to collect additional information 
to allow for a more complete assessment of these behaviors.
For this study, the C-SSRS is adapted for the assessment of the ideation and behavior categories 
only. The Intensity of Ideation and Lethality of Behavior sections are removed.
8.2.6.
Tuberculosis Testing and Monitoring
Tuberculosis testing at screening Visit 1
Medical history will determine the lifetime risk factors for TB infection, for TB progression, and 
for symptoms and/or signs of active TB.
A physical examination will determine symptoms of active TB, including measurement of 
body temperature (Section 8.2.2) and assessment of peripheral lymph nodes.
A chest x-ray (CXR) will be interpreted and reported by a radiologist or pulmonologist, as 
specified in the SoA (Section 1.3). Participants do not need to have a CXR at screening if results 
from a CXR within 3 months prior to the study are available.
All participants with no history of LTBI or active TB, and no history of positive Mantoux 
tuberculin skin test (TST) using purified protein derivative (PPD) or positive Mycobacterium 
tuberculosis interferon gamma release assay (IGRA), must have either a PPD TST or IGRA for 
M. tuberculosis.
PPD TST
An induration of 5 or more millimeters is considered positive in:

HIV-infected persons

persons with a recent contact with a person with TB disease

persons with fibrotic changes on chest radiograph consistent with prior TB

persons with organ transplants

persons who are immunosuppressed for other reasons (e.g., taking the equivalent of 
>15 mg/day of prednisone for 1 month or longer, taking TNF-α antagonists)
An induration of 10 or more millimeters is considered positive in all other potential clinical trial 
participants.
Two-step testing (repeat TST from 1 to 3 weeks after the first TST) is recommended for certain 
participant groups, including: 

persons receiving immunosuppressant treatment

persons with a history of temporally remote increased risk of TB infection

persons for whom the first test is negative, as per local public health and/or professional 
medical society recommendations.
IGRA for M. tuberculosis
Ensure that specimen handling, transport, timing, and laboratory procedures meet all 
requirements per package insert.

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Diagnosed LTBI
Participants diagnosed with LTBI are excluded (Section 5.2) unless they are candidates for LTBI 
treatment, are treated for LTBI, and the following criteria are met:

After receiving at least 4 weeks of appropriate LTBI therapy (as per WHO and/or 
the CDC guidelines), there is no evidence of hepatotoxicity (ALT/AST must 
remain ≤2 times ULN), or other treatment intolerance. 

The participant must continue and complete appropriate LTBI therapy in order to 
remain eligible to continue to receive study intervention.
Monitoring during the study
At a minimum, each participant will have the following documented at least every 3 months:

Thorough history to determine any risk factors for TB infection and for TB 
progression, symptoms, or signs of active TB, and

A thorough physical examination that includes assessment for signs of active TB, 
including measurement of body temperature and assessment of peripheral lymph 
nodes.
8.2.7.
Hepatitis B Testing and Monitoring
Initial testing for HBV infection includes hepatitis B surface antigen (HBsAg) and hepatitis B 
core antibody (anti-HBc).
If…
Then…
If HBsAg is positive
the participant is excluded 
If HBsAg is negative and anti-HBc is negative
the participant is not excluded
If HBsAg is negative and anti-HBc is positive
further testing for HBV DNA is required
If the screening HBV DNA is positive
the participant is excluded (see Section 5.2)
Participants who are hepatitis B core antibody-positive and HBV DNA-negative (undetectable) 
at Visit 1 are not excluded but will require HBV DNA monitoring every 3 months and at the 
participant’s last visit.
The following actions should be taken in response to HBV DNA test results.
If…
Then…
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 may resume according to the study schedule
If the participant has 2 or more test results with a value 
“below limit of quantitation” during the study
HBV DNA testing should be performed approximately 
once per month for the remainder of the study and 
referral to a hepatologist is recommended
If a result is obtained with a value “above limit of 
quantitation” at any time during the study
the participant will be permanently discontinued from 
the study intervention (see Section 7.1) and should be 
referred to a hepatology specialist immediately.
In selected cases, investigators may temporarily continue 
study intervention in accordance with current 
immunomodulator management in the setting of HBV 
DNA positivity. This option may be considered in 

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If…
Then…
consultation with the sponsor (or its designee) and after 
evaluation of individual participant’s risks and benefits.
8.2.8.
Hepatitis C Testing and Monitoring
Initial testing for HCV infection includes testing for antibodies to HCV. 
If…
Then…
If anti-HCV is positive
HCV RNA testing should be performed  
If HCV RNA test is negative
the participant is not excluded
If HCV RNA test is positive
the participant is excluded (see Section 5.2)
Participants who have had HCV infection and have been successfully treated, defined as a 
sustained virologic response (HCV RNA by PCR negative for at least 24 weeks following 
treatment completion) are not excluded on the basis of HCV as long as HCV RNA test is 
negative at screening.
If HCV RNA is detected during the study, the study drug will be permanently discontinued 
(Section 7.1), and the participant should receive appropriate follow-up medical care.
8.3.
Adverse Events and Serious Adverse Events
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or the study (see Section 7).
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All SAEs will be collected from the signing of the ICF until participation in study has ended.
All AEs will be collected from the signing of the ICF until participation in study has ended.
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the AE CRF.
Although all AEs after signing the ICF are recorded by the site in the CRF/electronic data entry, 
SAE reporting to sponsor begins after the participant has signed the ICF and has received study 
drug. However, if an SAE occurs after signing the ICF, but prior to receiving the study 
intervention, it needs to be reported ONLY if it is considered reasonably possibly related to study 
procedures.
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3, Appendix 3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 

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a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
sponsor.
8.3.1.1.
Adverse Event Monitoring with a Systematic Questionnaire
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 AE is serious or leads to discontinuation, it needs to be included on the AE form and the 
process for reporting SAEs is followed.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3, Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE
occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and AEs of special interest (AESIs) (as defined in 
Section 8.3.6), will be followed until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). Further information on 
follow-up procedures is provided in Section 10.3, Appendix 3.
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
8.3.5.
Pregnancy
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study intervention and until 8 weeks after the last dose.

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If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Section 10.4, Appendix 4.
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.6.
Adverse Events of Special Interest
Adverse events of special interest for this study include:

hypersensitivity

infusion site reactions

infections, and

malignancy.
Hypersensitivity
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data describing each symptom should be provided 
to the sponsor in the eCRF.  
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving study drug. It is recommended that participants 
who experience a systemic hypersensitivity reaction be treated per national and international 
guidelines.  
In the case of generalized urticaria or anaphylaxis, additional blood and urine samples should be 
collected as described in Section 10.6, Appendix 6, Recommended Laboratory Testing for 
Hypersensitivity Events. Laboratory results are provided to the sponsor via the central 
laboratory.
Infusion Site Reactions
Symptoms of a local infusion site reaction may include erythema, induration, pain, pruritus, and 
edema. If an infusion site event is reported, the AE will be recorded, and additional data will be 
provided to the sponsor in the eCRF.  
Infections
Participants will be monitored for symptoms and signs of infection after administration of 
LY3462817. More detailed information may be found in the IB.
Opportunistic Infections
The sponsor will identify infections considered to be opportunistic based on the publication 
“Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: 
consensus recommendations for infection reporting during clinical trials and postmarketing 
surveillance” (Winthrop et al. 2015).
Malignancy
Participants will be monitored for symptoms and signs of malignancy after administration of 
LY3462817. More detailed information may be found in the IB.

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8.3.7. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
trial intervention.
Sponsor collects product complaints on investigational products used in clinical studies in order 
to ensure the safety of study participants, monitor quality, and to facilitate process and product 
improvements.
Participants will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
NOTE: Adverse events/serious adverse events that are associated with a product complaint will 
also follow the processes outlined in Section 8.3.3 and Section 10.3, Appendix 3 of the protocol.
8.3.7.1.
Time Period for Detecting Product Complaints
Product complaints that result in an AE will be detected, documented, and reported to the 
sponsor during all periods of the study in which the intervention is used.
If the investigator learns of any product complaint at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a drug provided 
for the study, the investigator will promptly notify the sponsor.
8.3.7.2. Prompt Reporting of Product Complaints to Sponsor
Product complaints will be reported to the sponsor within 24 hours after the investigator becomes 
aware of the complaint.
The Product Complaint Form will be sent to the sponsor by the method designated by the 
sponsor. If the primary method is unavailable, the sponsor will designate an alternative method.
8.3.7.3.
Follow-up of Product Complaints
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the product complaint.
New or updated information will be recorded on the originally completed form with all changes 
signed and dated by the investigator and submitted to the sponsor.
8.4.
Treatment of Overdose
The signs and symptoms of LY3462817 overdose are not known. There is no known antidote for 
LY3462817 overdose.
In the event of an overdose, the investigator should contact the Medical Monitor immediately.
Hematology, chemistry, vital signs, and oxygen saturation should be monitored and supportive 
care should be provided as necessary.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.

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8.5.
Pharmacokinetics
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine the serum concentrations of LY3462817.
Samples may be drawn at additional time points during the study if warranted and agreed upon 
between both the investigator and sponsor. Instructions for the collection and handling of blood 
samples will be provided by the sponsor. The actual date and time of each sampling will be 
recorded.
LY3462817 concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Concentrations of LY3462817 will be assayed using a validated 
enzyme-linked immunosorbent assay method. Analyses of samples collected from 
placebo-treated participants are not planned.
Sample retention is described in Appendix 1, Section 10.1.12. During this time, samples 
remaining after the bioanalyses may be used for exploratory metabolism studies or exploratory 
analyses such as bioanalytical assay validation or cross-validation exercises.
8.6.
Pharmacodynamics
Samples for assessment of target engagement (RO and sPD-1) will be collected at the times 
specified in the SoA (Section 1.3). Sample retention is described in Appendix 1, Section 10.1.12.
Remaining samples may be used for additional exploratory studies to better understand 
LY3462817 and/or the disease.
8.7.
Genetics
A whole blood sample will be collected for genetic analysis where local regulations allow.
See Section 10.2, Clinical Laboratory Tests, and Section 1.3, the SoA for sample collection 
information.  
See Section 10.5, Genetics for genetic research, custody, and sample retention information.
8.8.
Biomarkers
See the SoA (Section 1.3) for the frequency of collection of the biomarker samples. 
Efficacy-related biomarkers
Certain biomarkers will be collected to evaluate their association with observed clinical 
responses to the study intervention. These biomarkers include:

hsCRP, and

ESR
RA characteristics biomarkers
The following biomarker samples will be collected to describe the disease characteristics of the 
randomized population:

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
Rheumatoid Factor, and

Anticyclic citrullinated peptide
Exploratory biomarkers
Serum, plasma, and whole blood RNA and DNA (to enable epigenetic analyses) samples will be 
collected at the times specified in the SoA (Section 1.3) where local regulations allow.
Samples may be used for research on the drug target, disease process, pathways associated with 
disease state, mechanism of action of LY3462817, and/or research method or in validating 
diagnostic tools or assay(s) related to RA.
Sample retention is described in Appendix 1, Section 10.1.12.
8.9.
Immunogenicity Assessments
All samples for immunogenicity should be taken predose when applicable at the visits and times 
specified in the SoA (Section 1.3). Venous blood samples will be collected and evaluated to 
determine antibody production against LY3462817. To interpret the results of immunogenicity, 
venous blood samples will be collected at the same time points to determine the concentrations 
of LY3462817. Antidrug antibodies may be further characterized for their ability to neutralize 
the activity of LY3462817.
Treatment-emergent antidrug antibody (TE-ADA) classifications are described in Section 9.4.6.
Sample retention is described in Appendix 1, Section 10.1.12.
8.10.
Health Economics
This section is not applicable for this study.

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9.
Statistical Considerations
9.1.
Statistical Hypotheses
The null hypothesis for the primary endpoint is that there is no difference between LY3462817 
and placebo in reducing the signs and symptoms of RA as measured by the mean change from 
baseline in DAS28-CRP at Week 12.
9.2.
Sample Size Determination
Approximately 80 participants will be randomly assigned to study intervention. At the 
completion of the study, approximately 40 participants will have been randomized to 
LY3462817 700 mg and 20 participants will have been randomized to LY3462817 300 mg and 
placebo during the double-blind treatment. All randomized participants in the modified 
intent-to-treat (mITT) population will be considered evaluable.
Assuming -1.80 and -0.75 as the DAS28-CRP change from baseline for LY3462817 700 mg and 
placebo, respectively, with standard deviation equal to 1.25, a 2-sided t-test with = 0.05 has 
greater than 80% power to detect a statistically significant difference in DAS28-CRP change 
from baseline at Week 12. The t-test provides an approximation to the power calculation for the 
primary analysis, which will use MMRM as described in Section 9.4.1. The comparison of 
LY3462817 300 mg and placebo for the DAS28-CRP change from baseline at Week 12 is 
exploratory, and therefore, no formal sample size calculation was performed for this comparison. 
Comparisons of LY3462817 700 mg and 300 mg for the DAS28-CRP change from baseline will 
also be considered exploratory, and again therefore, no formal sample size calculation was 
performed for this comparison.
9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Modified Intent-to-Treat (mITT)
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention. Participants will be analyzed according to the 
intervention to which they were assigned.
Safety
All participants randomly assigned to study intervention and who take at least 
1 dose of study intervention. Participants will be analyzed according to the 
intervention they actually received within each study period.
Pharmacokinetic (PK) Analysis
All participants randomly assigned to study intervention and who take at least 1 
dose of study intervention and have PK data available.

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9.4.
Statistical Analyses
9.4.1. General Considerations
Statistical analysis of this study will be the responsibility of sponsor or its designee. The 
independent variable, previous RA therapy population, is defined as only csDMARD 
experienced or bDMARD/tsDMARD experienced participants. Unless otherwise indicated in the 
statistical analysis plan (SAP), the analyses will be conducted as follows:
Analysis for
Description
Primary and secondary endpoint analyses 
comparing LY3462817 to placebo
Tested at a 2-sided level of 0.05 for frequentist analyses.
Adjustments for multiplicity
None to be performed since this a proof of concept Phase 2 study.
Baseline
Defined as the last available value before the first dose of study 
intervention for both efficacy and safety analyses. In most cases, this 
value will be what is recorded at the randomization visit (Visit 2).
Change from baseline
Will be calculated as the visit value of interest minus the baseline 
value.
Efficacy and patient-reported outcome 
(PRO) analysis 
Analysis models may contain the independent variables such as 
treatment group, baseline disease activity, and previous RA therapy 
population.
Endpoint analyses will use the mITT population unless otherwise 
specified.
Dichotomous responder endpoints
Missing data will be imputed using the nonresponder imputation (NRI) 
method.
Will be analyzed using a logistic regression model with treatment 
group, baseline disease activity, and previous RA therapy population
as model covariates.
NRI analysis
Participants will be considered nonresponders if:

they do not meet all the clinical response criteria

they are noncompliant with concomitant medication rules 
(Section 6.5)

they permanently discontinue study intervention at any time 
before the end of the treatment period for any reason, or

they are randomized and do not have at least 1 postbaseline 
observation.
Continuous efficacy endpoints
Mixed-effects model for repeated measures (MMRM) will be used.
The MMRM model will include treatment, strata (previous RA therapy 
population), baseline value, visit, treatment-by-visit interaction in the 
model as fixed factors, and patient as a random factor.
An unstructured covariance matrix will be used to model the 
within-subject errors. If this analysis fails to converge, other structures 
will be tested (in this order: Toeplitz, Autoregressive with 

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Analysis for
Description
heterogeneity, etc.).
The Kenward-Roger approximation will be used to estimate 
denominator degrees of freedom.
Significance tests will be based on least squares means and Type III 
tests.
Participant Disposition
A detailed description of participant disposition will be provided, 
including a summary of the number and percentage of participants 
entered into the study and randomized, and number and percentage of 
participants who complete the study or discontinue, both overall and 
by reason for discontinuation. A summary of important protocol 
deviations will be provided.
Participant Characteristics
Demographic data are collected and responded to demonstrate that the 
study population represents the target patient population. A summary 
of baseline participant characteristics, historical diagnoses, preexisting 
conditions, and prior therapies will be reported by treatment group 
using descriptive statistics. Other participant characteristics will be 
summarized by treatment group as deemed appropriate.
Concomitant Therapy
Previous and concomitant medications will be summarized by 
treatment group and will be presented by Anatomical Therapeutic 
Chemical drug classes using the latest version of the WHO drug 
dictionary.
Treatment Compliance
No analyses are planned to assess treatment compliance, given that 
participants will receive study intervention directly from the 
investigator or designee at the study site, under medical supervision 
(Section 6.4).
Additional imputation methods may be considered for all endpoint types.
Estimands for Double-Blind Treatment Period
Endpoints
Estimand  
strategy
Estimand 
description
Use post-
discontinuation 
data?
Imputation
Possible 
analysis 
method 
(estimator)
Primary 
endpoint and 
all other 
continuous 
efficacy and 
PRO 
endpoints
Hypothetical 
efficacy
Mean change 
from baseline 
(and mean 
scores) had all 
subjects 
remained on 
randomized
treatment.
No, only use 
data up until 
discontinuation
Participants who 
discontinue study 
intervention have 
remaining data imputed* to 
reflect the expected 
outcome had the subject 
remained on the study 
treatment without using 
restricted medications**
(assume missing at random 
[MAR])
MMRM model 
under MAR is 
applied to the 
data prior to 
treatment 
discontinuation
All 
dichotomous 
efficacy and 
Composite
responder
Proportion of 
responders 
where 
No, only data up 
until 
discontinuation 
Participants who start 
restricted medication** or 
discontinue study 
Endpoint 
definition 
effectively 

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Endpoints
Estimand  
strategy
Estimand 
description
Use post-
discontinuation 
data?
Imputation
Possible 
analysis 
method 
(estimator)
PRO 
endpoints
participants 
who start 
restricted 
medication or 
discontinue 
study 
intervention
are considered 
treatment 
failures
is required to 
define endpoint
intervention are defined as 
nonresponders
gives complete 
data
*Note: No actual imputed value per participant, mixed model used to derive result at treatment group level.
** Restricted medications include prohibited medications (Section 6.5.2) and permitted medications above the 
allowable dose range (Section 6.5.1).   
Any change to the data analysis methods described in the protocol will require an amendment 
only if the change affects a principal feature of the protocol. Any other change to the data 
analysis methods described in the protocol, and the justification for making the change, will be 
described in the SAP and the clinical study report (CSR). Additional exploratory analyses of the 
data will be conducted as deemed appropriate.
The SAP will be finalized prior to unblinding. It will include a more technical and detailed 
description of the statistical analyses described in this section.
9.4.2.
Primary Endpoint(s)
The primary endpoint is DAS28-CRP change from baseline at Week 12.
A restricted maximum likelihood based, MMRM analysis will be used to analyze the primary 
endpoint using the primary estimand as described in Section 9.4.1. 
9.4.3.
Secondary Endpoint(s)
Key secondary efficacy endpoints include the following at Week 12:

Proportion of participants achieving:
o
ACR20
o
ACR50, and
o
ACR70

Change from baseline in:
o
TJC
o
SJC
o
PhGADA_VAS (VAS)
o
PaGADA_VAS (VAS)
o
patient’s global assessment of arthritis pain (VAS), and
o
patient’s assessment of physical function (HAQ-DI)
o
SF-36

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
Change from baseline in mean score:
o
SDAI
o
CDAI
Continuous secondary endpoints will be analyzed using the model specified for the primary 
analysis described in Section 9.4.2. Dichotomous secondary endpoints will be analyzed using the 
logistic regression model described in Section 9.4.2. 
9.4.4.
Exploratory Endpoint(s)
Key exploratory efficacy endpoints include the following:

Proportion of participants at Week 12 achieving:
o
DAS28-CRP remission defined as DAS28-CRP <2.6 
o
DAS28-CRP LDA defined as DAS28-CRP ≤3.2
o
DAS28-ESR remission defined as DAS28-ESR <2.6 
o
DAS28-ESR LDA defined as DAS28-ESR ≤3.2
o
SDAI remission defined as SDAI ≤3.3
o
SDAI LDA defined as SDAI ≤11
o
CDAI remission defined as CDAI ≤2.8
o
CDAI LDA defined as CDAI ≤10

Change from baseline at Week 12 in the RAMRIS synovitis score from centrally read 
MRI images 

Measures of disease activity and PROs at all visits including mean scores, mean change 
from baseline, and proportion of participants achieving desired response
Details of exploratory analyses will be described in the SAP that is finalized before database 
lock.
9.4.5.
Pharmacokinetic/Pharmacodynamic Analyses
LY3462817 concentrations will be illustrated graphically and summarized descriptively. To 
facilitate the planning of future clinical studies, a model-based approach implemented using 
nonlinear mixed effects modeling (NONMEM) or other appropriate software may be conducted. 
Receptor occupancy data over time will be summarized by dose level. Exploratory PK/PD 
analyses may be conducted to evaluate the relationship between LY3462817 exposure and 
selected measures of response (for example, RO, sPD-1, clinical endpoints, and/or biomarkers). 
As appropriate, data from the present study may be combined with data from other studies in 
model-based analyses. 
Additional analyses may be conducted if deemed appropriate. Further details on PK and PK/PD 
analyses will be provided in the PK/PD analysis plan.
9.4.6.
Evaluation of Immunogenicity
Treatment-emergent antidrug antibodies (ADAs) are defined as participants

with a 2-fold (1 dilution) increase in titer than the minimum required dilution if no ADAs 
were detected at baseline (treatment-induced ADA) or 

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
with a 4-fold (2 dilutions) increase in titer compared with baseline if ADAs were detected 
at baseline (treatment-boosted ADA).
The frequency and percentage of participants with preexisting ADA and who are TE-ADA 
positive (TE-ADA+) to LY3462817 will be tabulated.   
For the TE ADA+ participants, the distribution of maximum titers will be described. The 
frequency of neutralizing antibodies, if assessed, may also be tabulated for the TE-ADA+ 
participants.
The relationship between the presence of antibodies and LY3462817 concentrations and PD 
response, including safety and efficacy, may also be assessed. Additional details may be 
provided in the SAP.
9.4.7.
Other Safety Analyses
Analyses/measures
Presented…
Safety analyses: AEs, SAEs, C-SSRS, vital 
signs, ECGs, and laboratory analytes
Descriptively summarized by treatment group, will use the safety 
population data
Categorical safety measures 
Summarized with counts by visit
Continuous safety measures
Summarized as mean change by visit
Exposure to study intervention
Calculated for each participant and summarized by treatment group 
by treatment period
Adverse events
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA) and summarized by system organ class, preferred term, severity, and relationship to 
the study intervention. All AEs, including pre-existing conditions, will be listed by participant, 
visit, preferred term, treatment group, severity, and relationship to the treatment.
Treatment-emergent adverse events
A TEAE is defined as an event that first occurred or worsened in severity after baseline, with 
baseline defined as all pre-existing conditions recorded at Visit 1 and any AEs recorded before 
the first dose of study intervention (that is, during the interval between Visits 1 and 2 and 
recorded with the time of onset before the first dose of study intervention). For events that are 
gender specific, the denominator and computation of the percentage will include only 
participants from the given gender.
The number and percentage of participants who experienced TEAEs, TEAEs by maximum 
severity, deaths, SAEs, TEAEs related to study intervention, discontinuations from the treatment 
due to an AE, and AESIs will be summarized. Treatment-emergent adverse events (all, by 
maximum severity), SAEs including deaths, and AEs that lead to treatment discontinuation will 
be summarized and analyzed by MedDRA system organ class and preferred term.
Treatment-related TEAEs (TEAEs related to study intervention) are defined as events that are 
indicated by the investigator on the eCRF to be related to treatment.
Adverse events of special interest will be identified by a standardized MedDRA query or a 
Lilly-defined MedDRA preferred term listing.

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Suicide-related thoughts and behaviors
Suicide-related thoughts and behaviors occurring during treatment will be summarized based on 
responses to the C-SSRS consistent with the C-SSRS Scoring and Data Analysis Guide 
(Columbia Lighthouse Project WWW).
Follow-up emergent adverse events
Follow-up emergent AEs, SAEs including deaths, and AEs that lead to study discontinuation will 
be summarized.
9.4.8.
Other Analyse(s) 
9.4.8.1.
Subgroup Analyses
Summaries of subgroups will be provided. Subgroup analyses may be conducted for the primary 
endpoint DAS28-CRP change from baseline using the mITT population.
Subgroups that may be evaluated include

previous RA therapy population

gender

race

geographic region

previous therapies, and

disease duration.
Detailed description of the summaries and/or statistical analyses are provided in the SAP.
9.4.8.2.
Supplemental Analyses
Supplemental analyses may be performed as deemed necessary.
9.5.
Interim Analyses 
Analyses for the primary database lock will be conducted as described in Section 9.4 when all 
participants have completed the double-blind treatment period or discontinued treatment.
One interim analysis of the safety and efficacy data be planned prior to database lock, to support 
planning activities. This will be done when approximately 40% to 60% of participants have 
completed Period 1 (double-blind treatment) or have discontinued treatment. Bayesian posterior 
probabilities will be calculated to assess the efficacy of LY3462817 700 mg versus placebo for 
DAS28-CRP for Period 1 at the interim analysis. The decision rules based upon the posterior 
probability results will help in deciding whether to support further clinical development of 
LY3462817. Additionally, this interim analysis will aid in the development of PK/PD modeling.
Other interim analyses may be conducted as needed. All interim analyses will be used to support 
planning activities associated with the clinical development program and to aid in the 
development of PK/PD modeling. Since the study may terminate early only for safety and/or 
futility, no adjustment of type I error will be performed. Information about interim futility and 
decision rules will be provided in the SAP.

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Internal assessment committee
Assessment of unblinded interim data will be conducted by an internal assessment committee 
(AC) with a limited number of prespecified members who do not have direct site contact or data 
entry or validation responsibilities (see Section 10.1.5, Appendix 1). Unblinding details will be 
specified in the unblinding plan section of the SAP or in a separate unblinding document.
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. Study sites will receive information about 
interim results only if they need to know for the safety of their participants.
Evaluation of unblinded safety data by the internal AC will occur if any of the following events 
are observed following review by the blinded safety review team:

three or more participants experience TEAEs in the same system organ class, and these 
TEAEs assessed as severe by the investigator and are judged as related to blinded study 
treatment by the investigator. 

a malignancy SAE occurs during the study.
Pending the evaluation by the internal AC, enrollment and/or further dosing may be stopped.
Unblinding during the interim analyses
Prior to any interim or the final database lock, a limited number of preidentified individuals may 
gain access to the unblinded data for internal decision making or to initiate the final population 
PK/PD model development processes for interim or final analyses. To minimize bias, the SAP 
and PK/PD analysis plan will be finalized and approved before any unblinding. Unblinding 
details will be specified in the SAP or in a separate unblinding document. Information that may 
unblind the study during the analyses will not be reported to study sites or to the blinded study 
team until the prespecified milestone for unblinding of study results. 
9.6.
Data Monitoring Committee (DMC)
Not applicable. An internal AC will be used to conduct the interim analysis (Section 9.5).
Overall committee structure information is in Section 10.1.5, Appendix 1. Details of the internal 
AC will be provided in the internal AC charter.

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10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines

Applicable ICH Good Clinical Practice (GCP) Guidelines

Applicable laws and regulations
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC annually or
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC

Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations
Investigator sites are compensated for participation in the study as detailed in the clinical trial
agreement.
10.1.2.
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study.

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10.1.3.
Informed Consent Process
The investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant or his/her legally authorized representative and answer all
questions regarding the study.
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center.
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study.
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative and is kept on file.
When rescreening is performed, the individual must sign a new ICF, repeat all screening 
procedures as described in the SoA (Section 1.3), and will be assigned a new identification 
number (see Section 5.4).
10.1.4.
Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets,
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
The sponsor has processes in place to ensure data protection, information security and data 
integrity. These processes include appropriate contingency plan(s) for appropriate and timely 
response in the event of a data security breach.
10.1.5.
Committees Structure
The internal AC will consist of a limited number of prespecified members not part of the blinded 
study team who do not have direct site contact or data entry or validation responsibilities. Further 
details will be provided in the internal AC charter.   

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10.1.6.
Dissemination of Clinical Study Data
A clinical study report will be provided for this study and a summary of study information 
provided on publicly available websites.
10.1.7.
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities, and requirements, including handling of noncompliance issues and monitoring 
techniques are provided in the Monitoring Plan.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.
The sponsor assumes accountability for actions delegated to other individuals (e.g., Contract 
Research Organizations).
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the Clinical Trial Agreement (CTA) 
unless local regulations or institutional policies require a longer retention period. No records may 
be destroyed during the retention period without the written approval of the sponsor. No records 
may be transferred to another location or party without written notification to the sponsor.
In addition, sponsor or its representatives will periodically check a sample of the participant data 
recorded against source documents at the study site. The study may be audited by sponsor or its 
representatives, and/or regulatory agencies at any time. Investigators will be given notice before 
an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 

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designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF.
Additionally, electronic Clinical Outcome Assessment (eCOA) data (participant-focused 
outcome instrument) will be directly recorded by the participant and investigator site personnel, 
into an instrument (for example, tablet). The eCOA data will serve as the source documentation 
and the investigator does not maintain a separate written or electronic record of these data.    
Data collected via the sponsor-provided data capture system(s) will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse.
Data from complaint forms submitted to sponsor will be encoded and stored in the global 
product complaint management system.
10.1.8.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available.
Definition of what constitutes source data can be found in Section 10.1.7.
10.1.9.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:
●
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines
●
Inadequate recruitment of participants by the investigator

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●
Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and assures
appropriate participant therapy and/or follow-up.
10.1.10.
Publication Policy
In accordance with the sponsor’s publication policy the results of this study will be submitted for 
publication by a peer-reviewed journal.
10.1.11.
Investigator Information
Physicians with a specialty in rheumatology and with other specialties and experience in 
treatment of patients with RA will participate as investigators in this clinical trial.
10.1.12.
Long-Term Sample Retention
Sample retention 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 the 
intervention or after the intervention becomes commercially available.
This table describes the retention period for potential sample types.
Sample Type
Custodian
Retention Period
After Last Participant Visit
Pharmacodynamic samples
Sponsor or designee
up to 7 years
Genetics sample
Sponsor or designee
up to 7 years
Exploratory Biomarker samples
Sponsor or designee
up to 15 years
Immunogenicity (ADA) sample
Sponsor or designee
up to 15 years
Pharmacokinetic (PK) sample
Sponsor or designee
up to 1 year
Abbreviations: ADA = antidrug antibody.

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10.2.
Appendix 2: Clinical Laboratory Tests
The tests detailed below will be performed by the central laboratory or by the local laboratory as 
specified in the table.
If the local laboratory results are used to make either a study intervention decision or response 
evaluation, the results must be entered into the CRF.
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5
of the protocol.
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations.
Pregnancy testing will be performed according to the SoA (Section 1.3).
Laboratory results that could unblind the study will not be reported to investigative sites 
or other blinded personnel.
Refer to Section 10.6, Appendix 6 for recommended laboratory testing for hypersensitivity 
events.
Clinical Laboratory Tests
Comments  
Hematology
Assayed by Lilly-designated laboratory
Hemoglobin
Hematocrit
Erythrocyte count (RBCs - Red Blood Cells)
Mean cell volume 
Mean cell hemoglobin
Mean cell hemoglobin concentration
Leukocytes (WBCs - White Blood Cells) 
Differential
   Neutrophils, segmented
   Lymphocytes
   Monocytes
   Eosinophils
   Basophils
Platelets
Cell Morphology (RBC and WBC)
Clinical Chemistry
Assayed by Lilly-designated laboratory
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin
Direct bilirubin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)

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Clinical Laboratory Tests
Comments  
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Blood urea nitrogen (BUN)
Creatinine 
Creatine kinase (CK)
Uric acid
Total protein
Glomerular filtration rate (GFR)
Only performed at screening
Albumin
Calcium
Phosphorus
Glucose
Cholesterol
Triglycerides
Urinalysis
Assayed by Lilly-designated laboratory
Specific gravity
pH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Blood
Nitrite
Urine leukocyte esterase
Microscopic examination of sediment
Hormones (female)
Serum Pregnancy
Assayed by Lilly-designated laboratory
Urine Pregnancy
Evaluated locally
Follicle stimulating hormone (FSH)
Assayed by Lilly-designated laboratory. Optional, performed 
as needed to confirm participant's postmenopausal status.
Serology
Assayed by Lilly-designated laboratory
Tuberculosis (TB) testing
See the protocol (Section 8.2.6) for more information about TB 
testing.
   QuantiFERON-TB Gold test   
Assayed by Lilly-designated laboratory. Testing can be 
performed by local laboratory if the site prefers.
   T-SPOT or TST
Evaluated locally
Human immunodeficiency virus (HIV) testing
Assayed by Lilly-designated laboratory
Hepatitis C virus (HCV) testing
   HCV antibody
Assayed by Lilly-designated laboratory. Will be confirmed 
with an additional testing method
Hepatitis B virus (HBV) testing
Assayed by Lilly-designated laboratory
   HBV DNA
Performed only for participants who test positive for anti-HBc

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Clinical Laboratory Tests
Comments  
Hepatitis B core antibody (Anti-HBc)
Hepatitis B surface antigen (HBsAg)
Pharmacokinetic Samples
LY3462817 concentration
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites
Flow Cytometry Panel
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
T cells, B cells, natural killer cells (TBNK)
Peripheral helper T cells
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Receptor occupancy
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Biomarkers
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
C-reactive protein, high-sensitivity (hsCRP)
Erythrocyte sedimentation rate (ESR)
Soluble programmed cell death ligand – 1 
(sPD-L1)
Soluble programmed cell death protein – 1 
(sPD-1)
Anti-cyclic citrullinated peptide (anti-CCP)
Rheumatoid factor (RF)
Immunoglobulin Panel 
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
IgG
IgM
IgA
Cytokine Panel
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Genetics sample
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Stored Samples
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Exploratory storage samples: 
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Serum
Plasma (EDTA)
Whole blood (EDTA) 
PAXgene (RNA) 
Immunogenicity Samples
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites.
Anti-LY3462817 antibodies 
Anti-LY3462817 antibodies neutralization

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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator (i.e., not related to progression of underlying 
disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdose should be reported regardless of sequelae.

“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments, which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

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
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been admitted to hospital for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle) which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting is 

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appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the above definition. These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse.
10.3.3.
Recording and Follow-Up of AE and/or SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to sponsor or designee in lieu of completion of the AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested by 
sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to sponsor or designee.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort and 
not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.

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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to sponsor or designee. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to sponsor or designee.

The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.

The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the sponsor or designee will request the investigator to provide a copy of any 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to sponsor or designee within 
24 hours of receipt of the information.
10.3.4.
Reporting of SAEs
SAE Reporting via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE will be the electronic data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

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
The site will enter the SAE data into the electronic system as soon as it becomes 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken off-
line, then the site can report this information on a paper SAE form (see next section) or to 
the sponsor by telephone.

Contacts for SAE reporting can be found in site training documents.
SAE Reporting via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the sponsor.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.

Contacts for SAE reporting can be found in site training documents.

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10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
Women
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Woman Not of Childbearing Potential
Women in the following categories are not considered WOCBP:
1. Premenarchal
2. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
3. Postmenopausal female is defined as, women with:

12 months of amenorrhea for women >55, with no need for follicle stimulating hormone 
(FSH)

12 months of amenorrhea for women >40 years old with FSH ≥40 mIU/mL and no other 
medical condition such as anorexia nervosa and not taking medications during the 
amenorrhea (e.g. oral contraceptives, hormones, gonadotropin releasing hormone, 
antiestrogens, selective estrogen receptor modulators [SERMs], or chemotherapy that 
induced amenorrhea)
Participation in the Study
Women of child-bearing potential may participate in this study.
Women of child-bearing potential participating must test negative for pregnancy prior to 
initiation of treatment as indicated by a negative serum pregnancy test at the screening visit 
followed by a negative urine pregnancy test prior to exposure. Women of child-bearing potential
must test negative for pregnancy prior to administration of the study drug intervention at each 
visit by a negative urine pregnancy test.
Women 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 

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lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual 
relationships with males.
All other WOCBP must agree to use 2 forms of effective contraception, where at least 1 form is 
highly effective (less than 1% failure rate), for the entirety of the study.  
Abstinence or contraception must continue following completion of study drug administration 
for at least 8 weeks or 5 half-lives, whichever is longer.
Acceptable Methods of Contraception
Highly effective methods of contraception (less than 1% failure rate) comprise, but are not 
limited to:

combination oral contraceptives 

implanted contraceptives, or 

intrauterine devices. 
Effective methods of contraception comprise but are not limited to male or female condoms with 
spermicide, diaphragms with spermicide, or cervical sponges.  
Not Acceptable Methods of Contraception
Use of male and female condoms as a double barrier method is not considered acceptable due to 
the high failure rate when these barrier methods are combined. 
Barrier protection methods without concomitant use of a spermicide are not an effective or 
acceptable method of contraception.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), 
declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable 
methods of contraception.
Men
Men, regardless of their fertility status, must agree to either remain abstinent (if this is their 
preferred and usual lifestyle) or use condoms as well as 1 additional highly effective (less than 
1% failure rate) method of contraception or effective method of contraception with nonpregnant 
WOCBP partners for the duration of the study and until their study drug concentrations are 
below the level that could result in a relevant potential exposure to a possible fetus, predicted to 
be 5 half-lives plus 90 days following the last dose of study intervention.  
Acceptable Methods of Contraception
Highly effective methods of contraception (less than 1% failure rate) comprise, but are not 
limited to:

combination oral contraceptives 

implanted contraceptives, or 

intrauterine devices. 
Effective methods of contraception comprise but are not limited to diaphragms with spermicide 
or cervical sponges.  

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Men and their partners may choose to use a double–barrier method of contraception that must 
include use of a spermicide.
Not Acceptable Methods of Contraception
Use of male and female condoms as a double barrier method is not considered acceptable due to 
the high failure rate when these barrier methods are combined. 
Barrier protection methods without concomitant use of a spermicide are not an effective or 
acceptable method of contraception.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), 
declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable 
methods of contraception.
Other Guidance
Men should refrain from sperm donation for the duration of the study and until their study drug
concentrations are below the level that could result in a relevant potential exposure to a possible 
fetus, predicted to be 5 half-lives plus 90 days following the last dose of study intervention.
Collection of Pregnancy Information
Male participants with partners who become pregnant
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention.
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also be 
followed to determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy will be 
reported including fetal status (presence or absence of anomalies) and indication for the 
procedure. 
Female Participants who become pregnant
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, including 
fetal status (presence or absence of anomalies) or indication for the procedure.

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While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at 
>20 weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any poststudy pregnancy related SAE considered reasonably related to the study intervention by 
the investigator will be reported to the sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention. If the participant is discontinued from the study intervention, the participant 
should remain in the study if possible and complete the posttreatment safety follow-up 
procedures detailed in the SoA (Section 1.3).  

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10.5.
Appendix 5: Genetics
Use/Analysis of DNA
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants.
DNA samples will be used for research related to LY3462817 or RA and related diseases. They 
may also be used to develop tests/assays including diagnostic tests related to LY3462817 and 
RA. Genetic research may consist of the analysis of 1 or more candidate genes or the analysis of 
genetic markers throughout the genome (as appropriate).
DNA samples will be analyzed for genetic variants thought to play a role in RA. Additional
analyses may be conducted if it is hypothesized that this may help further understand the clinical 
data.
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to LY3462817 or study interventions of this class to understand study disease or 
related conditions.
The results of genetic analyses may be reported in the CSR or in a separate study summary.
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
The samples will be retained while research on LY3462817 or study interventions of this class or 
RA continues but no longer than 7 years or other period as per local requirements.

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10.6.
Appendix 6:  Recommended Laboratory Testing for Hypersensitivity 
Events
Laboratory assessments should be performed if the participant experiences generalized urticaria 
or if anaphylaxis is suspected:

Collect sample after the participant has been stabilized, and within 1 to 2 hours of the 
event; however, samples may be obtained as late as 12 hours after the event as analytes 
can remain altered for an extended period of time. Record the time at which the sample 
was collected.

Obtain a follow-up sample at the next regularly scheduled visit or after 4 weeks, 
whichever is later.

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Hypersensitivity Tests
Notes
Selected test may be obtained in the event of anaphylaxis or systemic 
allergic/hypersensitivity reactions.
LY3462817 antidrug antibodies 
(immunogenicity/ADA)
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
LY3462817 concentrations (PK)
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
Tryptase
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
Note: If a tryptase sample is obtained more than 2 hours after the event 
(i.e., within 2 to 12 hours), or is not obtained because more than 12 hours 
have lapsed since the event, obtain urine sample for N-methylhistamine 
testing. Note that for tryptase serum samples obtained within 2 to 12 hours 
of the event, urine N-methylhistamine testing is performed in addition to 
tryptase testing. Collect the first void urine following the event. Obtain a 
follow-up urine for N-methylhistamine testing at the next regularly 
scheduled visit or after 4 weeks, whichever is later.
N-methylhistamine
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
Drug-specific IgE
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
Basophil activation test
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
NOTE: The basophil activation test is an in vitro cell-based assay that only 
requires a serum sample. It is a surrogate assay for drug-specific IgE but is 
not specific for IgE.
Complement (C3, C3a, and C5a)
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
Cytokine panel
Assayed by Lilly-designated laboratory. Results will not be provided to the 
investigative sites.
Abbreviations: ADA = antidrug antibody; IgE = immunoglobulin E; PK = pharmacokinetic.

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10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up 
Assessments
Close hepatic monitoring 
This table describes when close hepatic monitoring should occur.
If a participant with baseline results of...
develops the following elevations:
ALT or AST <1.5x ULN
ALT or AST ≥3x ULN
ALP <1.5x ULN
ALP ≥2x ULN
TBL <1.5x ULN
TBL ≥2x ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5x ULN
ALT or AST ≥2x baseline
ALP ≥1.5x ULN
ALP ≥2x baseline
TBL ≥1.5x ULN
TBL ≥2x baseline (except for participants with Gilbert’s syndrome)
The laboratory tests listed under Hepatic Evaluation and Testing below, including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase, should be repeated 
within 48 to 72 hours to confirm the abnormality and to determine if it is increasing or 
decreasing. 
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated medical monitor.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, including symptoms, recent illnesses (for example, heart failure, systemic infection, 
hypotension, or seizures), recent travel, history of concomitant medications (including 
over-the-counter), herbal and dietary supplements, and history of alcohol drinking and other 
substance abuse.
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and lab results stabilize. Monitoring of ALT, AST, ALP, and 
TBL should continue until levels normalize or return to approximate baseline levels. 
Comprehensive hepatic evaluation
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
1 or more of these conditions occur:
If a participant with baseline results of...
develops the following elevations:
ALT or AST <1.5x ULN
ALT or AST ≥3x ULN with hepatic signs/symptoms*, or ALT or 
AST ≥5x ULN
ALP <1.5x ULN
ALP ≥3x ULN 
TBL <1.5x ULN
TBL ≥2x ULN (except for participants with Gilbert’s syndrome) 
ALT or AST ≥1.5x ULN
ALT or AST ≥2x baseline with hepatic signs/symptoms*, or ALT or 
AST ≥3x baseline 
ALP ≥1.5x ULN
ALP ≥2x baseline 
TBL ≥1.5x ULN
TBL ≥1.5x baseline (except for participants with Gilbert’s syndrome)

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Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate
aminotransferase; TBL = total bilirubin level; ULN = upper limit of normal.
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%. 
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-international normalized ratio; 
tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal imaging 
study (for example, ultrasound or computed tomography scan).
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus, 
cytomegalovirus, Epstein-Barr virus, acetaminophen levels, acetaminophen protein adducts, 
urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl glucuronide, and 
serum phosphatidylethanol.
Based on the circumstances and the investigator’s assessment of the participant’s clinical 
condition, the investigator should consider referring the participant for a hepatologist or 
gastroenterologist consultation, magnetic resonance cholangiopancreatography, endoscopic 
retrograde cholangiopancreatography, cardiac echocardiogram, or a liver biopsy.
Additional hepatic data collection (hepatic safety CRF)
Additional hepatic safety data collection in hepatic safety CRFs should be performed in study 
participants who meet 1 or more of the following 5 conditions: 
If a participant with baseline...
has the following elevations…
ALT <1.5 ×ULN
ALT ≥5 × ULN on 2 or more consecutive blood tests 
ALP <1.5 × ULN
ALP ≥2 × ULN on 2 or more consecutive blood tests
TBL <1.5 × ULN
TBL ≥2 × ULN, except for cases of known Gilbert’s syndrome
ALT ≥1.5 × ULN
ALT ≥3 × baseline on 2 or more consecutive blood tests
ALP ≥1.5 × ULN
ALP ≥2 × baseline on 2 or more consecutive blood tests
TBL ≥1.5 × ULN
TBL ≥2 × baseline
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; TBL = total bilirubin level; 
ULN = upper limit of normal.
Note: The interval between the 2 consecutive blood tests should be at least 2 days.
Hepatic Evaluation Testing
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing. 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. 
Results will be reported if a validated test or calculation is available.

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Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs - red blood cells)
Alkaline phosphatase (ALP)
Leukocytes (WBCs - white blood cells)
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
    Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
    Lymphocytes
Creatine kinase (CK)
    Monocytes
Other Chemistry
    Basophils
Acetaminophen
    Eosinophils
Acetaminophen protein adducts
Platelets
Alkaline phosphatase isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl alcohol (EtOH)
Prothrombin time, international normalized ratio
(PT-INR)
Haptoglobin
Serology
Immunoglobulin A (IgA; quantitative)
Hepatitis A virus (HAV) testing:
Immunoglobulin G (IgG; quantitative)
    HAV total antibody
Immunoglobulin M (IgM; quantitative)
    HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatitis B virus (HBV) testing:
Urine Chemistry
    Hepatitis B surface antigen (HBsAg)
Drug screen
    Hepatitis B surface antibody (anti-HBs)
Ethyl glucuronide (EtG)
    Hepatitis B core total antibody (anti-HBc)
Other Serology
    Hepatitis B core IgM antibody
Antinuclear antibody (ANA)
    Hepatitis B core IgG antibody
Antismooth muscle antibody (ASMA)a
    HBV DNAd
Anti-actin antibodyb
Hepatitis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNAd
    EBV DNAd
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody
Hepatitis E virus (HEV) testing:
    CMV DNAd
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNAd
    HSV (Type 1 and 2) DNAd
Microbiologyc
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
a
Not required if antiactin antibody is tested.
b
Not required if antismooth muscle antibody (ASMA) is tested.
c
Assayed ONLY by investigator-designated local laboratory; no central testing available.
d
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.

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10.8.
Appendix 8: Provisions for Changes in Study Conduct During 
Exceptional Circumstances
In rare, exceptional circumstances, barriers may occur that prevent completion of mandatory 
visits at study sites.
When allowed by local regulations, remote visits performed by trained site personnel, including
telehealth (telephone or technology-assisted virtual) visits or visits at locations other than the site 
(e.g. participant’s home) performed by a mobile healthcare service provider, or alternate methods 
of study intervention delivery and administration may be considered as alternatives to replace 
on-site visits after consultation and written approval from the sponsor.
Once written approval is granted for changes in study conduct, additional written guidance will 
be provided by the sponsor.
The changes in study conduct captured in this Appendix will not be considered protocol 
deviations. Missing data will be captured as protocol deviation(s). Such changes are intended to 
mitigate risks of participants missing visits, allow participants to continue safely in the study, and 
maintain the data integrity of the study. Good Clinical Practice compliance and minimization of 
risk to study integrity are important considerations. Ensuring the safety of study participants is 
the prevailing consideration.
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. Changes in study conduct not 
described in this appendix, or not consistent with applicable local regulations, are not allowed.
Informed Consent and Ethical Review Boards
Additional written consent from the participant will be obtained for those who participate in 
mobile health services, and a method of study intervention administration other than on-site 
visits. The site should also document the participant’s verbal consent for having telehealth visits 
and alternate study intervention delivery prior to implementation of these activities.
Ethical review boards and regulatory bodies will be notified as soon as possible to communicate 
implementation of changes in study conduct due to exceptional circumstances. To protect the 
safety of study participants, urgent changes may be implemented before such communications 
are made, but all changes will be reported as soon as possible following implementation.
Study Intervention Administration
In cases when a participant is unable to come to the site to receive study intervention during 
normal on-site visit, the site should work with the sponsor to determine appropriate actions to 
administer the study intervention to the participant. This may include administration of study 
intervention to the participant during a mobile health visit, provided these requirements are met 
prior to administration of intervention:
1. sponsor approves the alternative method to on-site administration, taking local regulatory 
requirements into consideration
2. participant consent must include provision of any personal information

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3. delivery of intervention does not compromise treatment blinding and ensures product 
integrity. The existing protocol requirements for product accountability remain 
unchanged 
4. investigator/sponsor provides oversight of the transport process to ensure accountability 
and product quality (i.e., storage conditions and intact packaging upon receipt)
5. only authorized study staff or designee may supply or administer study intervention, and
6. resuscitation equipment, emergency drugs, and appropriately trained medical staff must 
be available during the infusion and for at least 1 hour after the completion of the 
infusion, in case of hypersensitivity or infusion site reactions.
Concomitant medications may be recorded during a remote visit.
Study Assessments and Procedures
Remote visits to complete appropriate assessments are acceptable. Site staff should capture the 
visit location and method with a specific explanation for any possible data missing in the source 
document and eCRF.
Visit Windows
Every effort should be made for the participant to return to on-site visits as soon as reasonably 
possible, while ensuring the safety of the participant and investigational site staff. 
Except for Visits 6 and 7, flexibility in visit windows can be considered following consultation 
with and prior approval by the sponsor.
Efficacy Assessments
Conduct or review of participant-reported outcomes may be completed during a telehealth visit.
These activities and health care professional RA evaluations, including assessments of the 
disease activity by a blinded assessor, may be conducted during a mobile health visit.
Safety Assessments
Adverse events/serious adverse events, product complaints, and C-SSRS-related assessments 
need to be completed during a telehealth visit. These activities and physical examinations may be 
completed during a mobile health visit.
Requirements related to the reporting of SAEs remain unchanged. 
Sample Collection
In exceptional circumstances, to ensure participant safety and with the sponsor’s prior written 
approval, local laboratory testing may be conducted in lieu of central laboratory testing only if it 
is determined that central laboratory testing cannot be conducted. The local laboratory must also 
be qualified in accordance with applicable local regulations. Clinically significant laboratory 
findings must be recorded as an AE in the AE CRF.
Documentation of Changes to Study Conduct
Sites must identify and document the details of how all participants, visits, methods, and 
activities conducted were affected by exceptional circumstances. 
Consent to be obtained and documented as above.  

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Source document(s) that are generated at the participant’s home or any remote location should be 
part of the investigator’s source documentation and should be transferred to the site in a secure 
and timely manner. 
Missing Data and Other Protocol Deviations
Sites should capture specific explanations for any missing data and other protocol deviations in 
source documents, eCRFs, and other data capture systems. While protocol deviations may be 
unavoidable in an exceptional circumstance, documentation of deviations and missing data will 
be important for data analysis and reporting.

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10.9.
Appendix 9: Abbreviations
Term
Definition
AC
assessment committee
ACR
American College of Rheumatology
ACR20
20% improvement in American College of Rheumatology criteria
ACR50
50% improvement in American College of Rheumatology criteria
ACR70
70% improvement in American College of Rheumatology criteria
ADA
antidrug antibody
AE
adverse event
AESI
adverse event of special interest
AIDS
acquired immune deficiency syndrome
ALT
alanine aminotransferase
ALP
alkaline phosphatase
anti-HBc
hepatitis B core antibody
AST
aspartate aminotransferase
BCG
Bacillus Calmette-Guerin
bDMARD
biologic disease-modifying antirheumatic drug
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the participant is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the participant are not.
A double-blind study is one in which neither the participant 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.
CBD
cannabidiol
C-CASA
Columbia Classification Algorithm of Suicide Assessment
CDAI
Clinical Disease Activity Index
CDC
United States Centers for Disease Control and Prevention
CIOMS
Council for International Organizations of Medical Sciences
Companion diagnostic 
An in vitro diagnostic device (assay or test) that provides information that is essential 
for the safe and effective use of a corresponding therapeutic product

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complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, GCP, and applicable regulatory requirements.
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRP
C-reactive protein
csDMARD
conventional synthetic disease-modifying antirheumatic drug
CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
CTA
Clinical Trial Agreement
CXR
chest x-ray
DAS28-CRP
Disease Activity Score - C-reactive protein
DAS28-ESR
Disease Activity Score - erythrocyte sedimentation rate
DAS28-hsCRP
Disease Activity Score - high sensitivity C-reactive protein
Device Deficiencies
Equivalent to product complaint
DMARD
disease-modifying antirheumatic drug
DMC
data monitoring committee
ECG
electrocardiogram
eCOA
electronic Clinical Outcome Assessment
eCRF
electronic case report form
EDC
electronic data capture system
enroll
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment.
enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
ESR
erythrocyte sedimentation rate
EULAR
European League Against Rheumatism
FDA
Food and Drug Administration

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FSH
follicle stimulating hormone
GCP
Good Clinical Practice
Gd-DTPA
gadolinium diethylenetriamine penta-acetic acid
HAQ-DI
Health Assessment Questionnaire-Disability Index
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
hsCRP
high sensitivity C-reactive protein
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committees
Ig
immunoglobulin
IGRA
interferon gamma release assay
IL
interleukin
IMP
Investigational Medicinal Product
Informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed and dated informed consent form.
INR
international normalized ratio
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
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 Boards

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IV
intravenous
IWRS
interactive web-response system
LDA
low disease activity
LTBI
latent tuberculosis infection
MAR
missing at random
MedDRA
Medical Dictionary for Regulatory Activities
Medical monitor
Individual responsible for the medical conduct of the study. Responsibilities of the 
medical monitor may be performed by a clinical research physician, clinical research 
scientist, global safety physician, or other medical officer designated by the sponsor.
mITT
modified intent-to-treat
MMRM
mixed-effects model for repeated measures
MRI
magnetic resonance imaging
MTX
methotrexate
NIMP
Noninvestigational Medicinal Product
NONMEM
nonlinear mixed effects modeling
NRI
nonresponder imputation
NSAID
nonsteroidal anti-inflammatory drug
OMERACT
Outcome Measures in Rheumatoid Arthritis Clinical Trials
PaGADA_VAS
Patient’s Global Assessment of Disease Activity
participant
Equivalent to Clinical Data Interchange Standards Consortium (CDISC) term “subject”: 
an individual who participates in a clinical trial, either as recipient of an investigational 
medicinal product or as a control.
PCR
polymerase chain reaction
PD-1
programmed cell death protein 1
PD-L1
programmed cell death ligand 1
PhGADA_VAS
Physician’s Global Assessment of Disease Activity
PK/PD
pharmacokinetics/pharmacodynamics
PPD
purified protein derivative
PR
pulse rate

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PRO
patient-reported outcomes
Q4W
once every 4 weeks
RA
rheumatoid arthritis
RAMRIS
Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system
RO
receptor occupancy
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SDAI
Simplified Disease Activity Index
SERM
selective estrogen receptor modulators
SF-36
Medical Outcomes Study 36-Item Short Form Health Survey
SJC
Swollen Joint Counts
SoA
Schedule of Activities
sPD-1
soluble programmed cell death protein 1
TB
tuberculosis
TBL
total bilirubin level
TE-ADA
treatment-emergent antidrug antibody
TE-ADA+
treatment-emergent antidrug antibody positive
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, and does not necessarily have to have a causal relationship 
with this treatment.
TJC
Tender Joint Counts
TNF-α
tumor necrosis factor-α
tsDMARD
targeted synthetic disease-modifying antirheumatic drug
TST
tuberculin skin test
ULN
upper limit of normal

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VAS
visual analog scale
WHO
World Health Organization
WOCBP
woman of childbearing potential

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10.10.
Appendix 10:  Country Specific Requirements  
Discontinuation of Inadvertently Enrolled Patients in the United Kingdom 
If the sponsor or investigator identifies a participant who did not meet enrollment criteria and 
was inadvertently enrolled, then the participant should be discontinued from study treatment and 
safety follow up should be performed as outlined in Section 1.3 (Schedule of Activities), 
Section 8.3 (Adverse Events and Serious Adverse Events), and Section 8.2 (Safety Assessments) 
of the protocol.

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11.
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